Breaking Antibiotic Dependency in Aquaculture: Evaluating Alternative Disease Management Strategies for Sustainable Aquaculture in Bangladesh

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Naim Mahmud, Md. Zihad Rahman Jony, Sanchari Sakidar, Neaz A. Hasan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9386222/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The rapid expansion of aquaculture in Bangladesh has substantially increased national fish production but has simultaneously intensified dependence on antibiotics for disease prevention and treatment, thereby accelerating the emergence and dissemination of antimicrobial resistance (AMR). This review critically evaluates the current landscape of antibiotic use, AMR prevalence, and the potential of non-antibiotic disease management strategies to foster sustainable and antibiotic-sparing aquaculture systems in Bangladesh. A structured evidence synthesis was conducted following the Joanna Briggs Institute guidance, drawing on peer-reviewed and gray literature published. The synthesis reveals widespread empirical and often unregulated antibiotic application across freshwater and brackish-water systems, accompanied by high frequencies of multidrug-resistant bacterial isolates and detectable antibiotic residues in cultured fish and surrounding environments. These patterns underscore significant risks to food safety, ecosystem integrity, and public health. In contrast, a broad spectrum of alternative approaches, including probiotics, prebiotics, synbiotics, phytobiotics, immunostimulants, vaccines, and nanoparticle-based interventions, demonstrate strong experimental efficacy in enhancing host immunity, modulating gut microbiota, reducing pathogen load, and improving survival and growth metrics. An adapted technology readiness perspective indicates that probiotics and synbiotics possess the highest practical maturity, whereas phytobiotics and immunostimulants show promising but inconsistent field performance, and nanotechnology-based solutions largely remain at pilot or laboratory stages in Bangladesh. The principal barrier to transition is therefore not scientific insufficiency but institutional and policy fragmentation. Strengthening fish health diagnostics, reforming regulatory oversight of aquaculture therapeutics, expanding farmer-centric extension services, and prioritizing field-scale validation and cost–benefit analyses are essential to reduce antibiotic dependency. Integrating scientific innovation with coordinated policy and capacity development offers Bangladesh a viable pathway toward environmentally sustainable, economically resilient, and public-health-protective aquaculture production. Antimicrobial resistance (AMR) Antibiotic alternatives Fish health management Probiotics and immunostimulants Sustainable aquaculture Figures Figure 1 Figure 2 1. Introduction Antibiotics are widely recognized as effective therapeutic agents for the treatment of infectious diseases (Afroze et al., 2025 ). The broader term “ antimicrobials ” encompasses antibacterial, antifungal, antiparasitic, and antiviral agents (Leekha et al., 2011 ), among which antibiotics play a central role by inhibiting bacterial growth or eliminating pathogenic bacteria. These compounds are therefore essential in both human and veterinary medicine for the management of infectious diseases (Done et al., 2015 ). However, the extensive and often indiscriminate use of antibiotics has accelerated the emergence of antimicrobial resistance (AMR), now recognized as one of the most severe global public health threats. A global systematic analysis estimated that 1.27 million deaths were directly attributable to bacterial antimicrobial resistance, while 4.95 million deaths were associated with resistant infections worldwide in 2019, with projections suggesting that this figure could rise to approximately 10 million deaths per year by 2050 if effective mitigation strategies are not implemented (Murray et al., 2022 ; Salam et al., 2023 ; Ahmed et al., 2024 ). Beyond health impacts, AMR poses substantial economic risks. According to World Bank projections, under a high-impact AMR scenario, global gross domestic product (GDP) could decline by 3.8% by 2050, with an estimated annual economic loss of USD 3.4 trillion by 2030 (World Bank, 2017). Antibiotic resistance also undermines the safety and feasibility of critical medical interventions, including surgical procedures, cancer chemotherapy, and organ transplantation, all of which rely heavily on effective antimicrobial prophylaxis (Ahmed et al., 2024 ; Ho et al., 2024 ). The rapid spread of antibiotic resistance is largely attributed to the overuse and misuse of antibiotics across multiple sectors, including human healthcare, agriculture, animal husbandry, and food production systems (Ahmed et al., 2024 ). Globalization further exacerbates this challenge by facilitating the transboundary dissemination of resistant bacteria and resistance genes, thereby posing risks even to regions with relatively prudent antibiotic use practices (Laxminarayan et al., 2013 ; Stein et al., 2014; Barlam and Gupta, 2015 ). Alarmingly, several pathogenic bacteria of major human health concern, including Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii , and Pseudomonas aeruginosa , have already developed resistance to multiple, and in some cases many, classes of antibiotics, posing a serious challenge to effective clinical treatment (Murray et al., 2022 ; WHO, 2017; Afroze et al., 2025 ). Against this backdrop, aquaculture has been identified as an emerging pathway for the development and dissemination of antimicrobial resistance (AMR), especially in low- and middle-income countries where regulatory frameworks, antibiotic stewardship, and surveillance systems are often fragmented or insufficiently implemented (FAO, 2021 ; Cabello et al., 2016 ). The rapid expansion of aquaculture has been driven by increasing global demand for animal protein, declining wild fish stocks due to overfishing and pollution, and the need to ensure food security for a growing human population (Alfiko et al., 2022 ; Fantatto et al., 2024 ; Mahmud et al., 2025 ). Since 1990, global aquaculture production has increased by more than 650%, reaching a record 130.9 million metric tons (MT) in 2022, of which 94.4 million MT comprised aquatic animals (FAO, 2024; Ritchie, 2019 ). Asia accounts for over 91% of global aquaculture production (FAO, 2024). However, intensified farming practices aimed at maximizing productivity often increase susceptibility to bacterial, viral, fungal, and parasitic diseases, thereby promoting reliance on chemotherapeutic agents, including antibiotics (Salma et al., 2022 ). While antibiotics have historically supported productivity in aquaculture, practices such as prophylactic use, nonprescription access, incorrect dosing, and inadequate compliance with withdrawal periods have raised significant ecological and public health concerns (Chowdhury et al., 2022 ; Kawsar et al. 2022 ). Antibiotic residues can accumulate in aquatic environments and in fish tissues, and continuous exposure can create selective pressure that favors the emergence and persistence of resistant microbial populations (Bhat et al., 2022 ). Furthermore, the horizontal transfer of antibiotic resistance genes among aquatic bacteria may increases the likelihood of resistance transmission to human pathogens, amplifying risks across the food–environment–health nexus (Jeon et al., 2023 ). Bangladesh represents a particularly important case study within this global context. As one of the world’s leading fish-producing nations, Bangladesh recorded total fish production of 5.018 million MT in 2023–2024, with aquaculture accounting for 59.34% of national output (DoF, 2023). Over the past three decades, aquaculture has become one of the fastest-growing agro-food sectors in the country. Inland aquaculture production more than doubled from 1.006 million MT in 2007–08 to 2.852 million MT in 2022–23 (DoF, 2023; Haque and Mahmud, 2025 ). This rapid expansion has been reported to be influenced by widespread use of veterinary drugs and aqua-medicines, often driven by farmers’ preferences, disease pressure, and market availability rather than evidence-based guidelines. Consequently, antibiotic-resistant bacteria have been widely reported in aquaculture environments, cultured fish, and surrounding water bodies in Bangladesh, raising concerns for food safety, ecosystem health, and consumer protection (Salma et al. 2025 ; Ahmed et al., 2019 ; Chowdhury et al. 2022 ; Khan et al., 2022 ; Ripon et al., 2023 ; Nayem et al., 2025 ). The detection of antibiotic residues in export-oriented aquaculture products further threatens international market access and compliance with stringent food safety regulations, potentially undermining the economic sustainability of the sector. In response to these challenges, alternative disease management strategies have gained increasing attention as sustainable approaches to reduce antibiotic dependency and mitigate AMR risks in aquaculture. These strategies include the use of probiotics, prebiotics, phytobiotics, immunostimulants, vaccines, bacteriophages, and improved biosecurity and farm management practices (Bondad-Reantaso et al., 2023 ; Elgendy et al., 2024 ; Rahayu et al., 2024 ; AlQurashi et al., 2025 ; Rasul et al., 2025 ). Such interventions aim to enhance host immunity, stabilize microbial communities, and prevent disease outbreaks with reduced risk of selecting for antibiotic resistance compared with antibiotics that drive antimicrobial resistance. Nevertheless, their effectiveness and adoption remain highly variable, influenced by species-specific responses, culture systems, environmental conditions, regulatory frameworks, and socio-economic constraints (Mahmud et al., 2025 ). Despite the growing body of global literature on antibiotic alternatives in aquaculture, evidence specific to Bangladesh remains fragmented and insufficiently synthesized. There are a few comprehensive reviews that critically evaluate the efficacy, feasibility, and limitations of non-antibiotic disease management strategies within Bangladeshi aquaculture systems, while simultaneously considering farmer-level adoption barriers, regulatory challenges, and economic implications. Therefore, this review aims to systematically synthesize existing knowledge on alternatives to antibiotics in the aquaculture sector of Bangladesh. Specifically, it evaluates the effectiveness of non-antibiotic disease control strategies, assesses their potential to reduce AMR risks, and identifies key research gaps and practical constraints hindering large-scale implementation. By integrating scientific evidence with policy and management perspectives, this review seeks to support the development of sustainable, antibiotic- sparing aquaculture systems in Bangladesh. 2. Methodology This review was conducted following the methodological guidance of the Joanna Briggs Institute (JBI) for evidence synthesis in scoping reviews (Peters et al., 2020 ). The JBI framework was adopted to ensure methodological transparency and systematic identification of relevant literature. The review aimed to synthesize existing evidence on alternative disease management strategies to reduce antibiotic dependency in aquaculture systems of Bangladesh, guided by predefined inclusion and exclusion criteria and a structured search strategy (Mahmud and Haque, 2025 ). 2.1 Literature Search Strategy A comprehensive literature search was conducted to identify relevant peer-reviewed and grey literature on alternative disease management strategies in aquaculture. Electronic database searches were performed in PubMed, Scopus, Web of Science, and ScienceDirect, while Google Scholar was additionally used to capture relevant studies not indexed in major databases. The search strategy integrated controlled vocabulary (e.g., MeSH terms in PubMed) and free-text keywords combined using Boolean operators, with database-specific syntax applied to improve search sensitivity and precision. The final search was completed on 15 February 2025. In Scopus, the search string TITLE-ABS-KEY (aquaculture OR “fish farming” OR “shrimp culture”) AND TITLE-ABS-KEY (“antibiotic alternatives” OR probiotics OR prebiotics OR phytobiotics OR vaccines OR immunostimulants OR biosecurity OR “disease management”) AND TITLE-ABS-KEY (Bangladesh OR “tropical aquaculture” OR “developing countries”) was used to ensure reproducible retrieval of relevant studies. Grey literature was identified through targeted searches of reports and policy documents from international and national organizations, including the Food and Agriculture Organization (FAO), World Health Organization (WHO), and the Department of Fisheries (DoF), Bangladesh, as well as relevant NGO publications. 2.2 Inclusion and Exclusion Criteria To ensure the relevance, quality, and applicability of the selected literature, studies were screened using predefined eligibility criteria (Table 1 ). Table 1 The study’s eligibility and exclusion criteria (followed by Gambelli et al. 2019 ) Criterion Description Inclusion Exclusion Timeframe After 2000 Before 2000 Type of Language English Non-English Type of Literature Peer-reviewed literature, government, and organizational reports News articles and non-scientific web content lacking analytical or empirical basis Area of Content Studies addressing non-antibiotic disease management strategies in aquaculture, including probiotics, prebiotics, phytobiotics, immunostimulants, vaccines, nanoparticles, biosecurity measures, and integrated health management approaches Non-aquaculture sectors (e.g., terrestrial agriculture, livestock, poultry) Publication Status Published and available online Published but not accessible Geographic Coverage Aquaculture-producing countries were included to derive comparative insights and identify disease management strategies applicable to Bangladeshi aquaculture. None Outcome Reporting Disease resistance, survival, growth performance, environmental sustainability, economic feasibility, or farm-level applicability Studies lacking clear outcome indicators Methodologies Studies employing experimental, observational, and field-based methods. Studies with unclear design, insufficient methodological detail, or unsupported claims. 2.3 Data Extraction Data were extracted from the selected studies using bibliographic details (authors, year of publication, journal), study location, culture system, and target species. Methodological characteristics were recorded, including the study design (experimental, observational, field trial, or review), the type of disease management strategy evaluated, and the duration of interventions. Outcome variables extracted encompassed indicators of fish health and performance (e.g., disease incidence, survival rate, immune response, growth performance), environmental impacts, economic feasibility, and practical constraints related to implementation. Quantitative and qualitative findings were synthesized using narrative and thematic approaches to evaluate the effectiveness and applicability of alternative disease management strategies across studies. 2.4 Categorization and Synthesis of Evidence The extracted data were categorized based on the type of alternative disease management strategy, including probiotics and prebiotics, phytobiotics, immunostimulants, vaccines, nanoparticles, and improved biosecurity and farm management practices. Evidence synthesis involved a comparative evaluation of the effectiveness and limitations of each approach within the context of Bangladeshi aquaculture. The effectiveness was assessed based on the reported direction and magnitude of outcomes, including changes in disease incidence, survival rate, growth performance, and immune response indicators. Emphasis was placed on identifying patterns, consistencies, and discrepancies across studies, while highlighting system-specific and species-specific responses. 2.5 Critical Analysis and Interpretation A critical appraisal of the synthesized literature was conducted to evaluate the scientific robustness, practical relevance, and contextual applicability of alternative disease management strategies in aquaculture. The analysis emphasized nutritional and immunological benefits, host sensitivity to pathogen exposure, environmental sustainability, and scalability at the farm level. Particular attention was given to how these alternatives align with existing farmer practices, regulatory frameworks, and resource constraints in Bangladesh. To contextualize the maturity and real-world applicability of antibiotic alternative interventions, an adapted Technology Readiness Level (TRL) framework was applied. Interventions were classified along a qualitative scale from early conceptual or laboratory validation (TRL 1–3), controlled pilot or experimental farm testing (TRL 4–5), field-scale demonstration and partial farmer adoption (TRL 6–7), to commercially established and widely implemented practices (TRL 8–9) (Mankins, 1995 ; Yfanti, and Sakkas, 2024 ; Balafoutis et al. 2020 ). The TRL assignment was based on reported evidence regarding validation scale, regulatory or commercial availability, and documented adoption in aquaculture systems. To ensure consistency, predefined decision criteria were applied, and interventions were comparatively assessed across studies describing similar implementation contexts. Based on this integrated assessment, key research gaps, institutional bottlenecks, and implementation challenges were identified. These insights were used to highlight priority areas for future research, policy refinement, and capacity development, supporting a structured transition toward sustainable, antibiotic-sparing aquaculture health management in Bangladesh. 3. Antibiotic Use in Aquaculture of Bangladesh Intensive aquaculture practices in Bangladesh are characterized by high stocking densities, sub-optimal hygienic conditions, and multiple physical and environmental stressors, including overcrowding, frequent handling and transportation, predation pressure, inappropriate lighting and noise exposure, and fluctuating water quality parameters such as pH, temperature, dissolved oxygen, nitrite, and turbidity (Chowdhury et al., 2022 ). These stressors weaken fish's immune responses and increase their susceptibility to infectious diseases. The presence of emerging pathogens and their intensification has led to a widespread dependence on antimicrobials, particularly antibiotics, for disease prevention and control. Antibiotics are commonly applied as therapeutic and prophylactic agents to reduce disease-induced mortality and prevent bacterial infections in Bangladesh. These compounds are often administered directly into pond water or applied as top-coated formulations on commercial fish feeds (Mahmud et al., 2025 ; Okocha et al., 2018 ). However, the improper and unregulated use of antibiotics has raised significant concerns about antimicrobial resistance, environmental contamination, and food safety. Numerous studies have reported the presence of antibiotic residues in aquaculture environments and farmed fish products. The most commonly detected antibiotics in aquaculture water are tetracyclines, macrolides, fluoroquinolones, and sulfonamides (Afroze et al., 2025 ) (Table 2 ). Residues of trimethoprim, sulfamethoxazole, norfloxacin, and oxytetracycline acid have been detected in shrimp ponds, sediments, and adjacent canals (Haque et al., 2023 ; Barman et al., 2018 ). Hasan et al. ( 2022 ) reported oxytetracycline (OTC) residues in live fish and transport water samples collected from markets in Mymensingh district, Bangladesh. OTC was detected in 13 fish and 5 water samples during summer and in 8 fish samples during winter, with overall residue positivity of 5.42% in fish and 8.33% in water. Concentrations in fish ranged from 10.80 to 77.55 ppb, with the highest prevalence observed in pangas (16.67%). Chowdhury et al. ( 2022 ) reported that 71% of fish farms in Mymensingh, Cumilla, Bagerhat, Jashore, Khulna, and Satkhira used antibiotics during the production cycle, with oxytetracycline, ciprofloxacin, and amoxicillin being the most commonly used, often applied without prescription. Region-specific investigations further highlight the scale and diversity of antibiotic use across the country. Kawsar et al. ( 2022 ) documented the use of 30 different antibiotics under multiple trade names in fish farms in the Narsingdi region, with oxytetracycline (26%), erythromycin (19%), and sulfamethoxazole (17%) being the most commonly applied active ingredients, followed by ciprofloxacin (14%), enrofloxacin (9%), chlortetracycline (6%), and amoxicillin (5%). In shrimp farms of the south-western coastal region, commonly used antibiotics included oxytetracycline, chlortetracycline, amoxicillin, co-trimoxazole, sulphadiazine, and sulphamethoxazole (Shamsuzzaman and Biswas, 2012 ). In contrast, studies from south-eastern districts such as Cumilla, Chandpur, and Feni identified erythromycin, oxytetracycline, chlortetracycline HCl, and doxycycline as the most frequently used antibiotics in aquaculture operations (Hossain et al., 2021 ). Table 2 Antibiotics used in the Aquaculture of Bangladesh in different regions (Adopted from Bari et al. 2024; Rasul et al. 2025 ; Salma et al. 2022 ; Kawsar et al. 2022 ) Brand Name Active Ingredients Dose Producers Cipro-Avet Ciprofloxacin 0.05 mL/1–2 kg feed ACME Laboratories Ltd Ciproflox Ciprofloxacin hydrochloride 250 mg/1–2 kg of feed SK + F Ltd. Levoflox Levofloxacin 6.61 mg/L of water for 3–5days Drug International Ltd. Micronid Erythromycin, sulfadiazine, trimethoprim 5000 mg/kg feed for 3–5 days Renata Ltd. Neomin-50 Neomycin sulphate 500 mg/1–1.5 L of water Local supplier Oxy-D vet Oxytetracycline-20% Doxycyline-10% 5000–10,000 mg/kg body weight of fish for 5–7 days Eon Animal Health Products Ltd. Oxysenthin 20% Oxytetracycline HC1 BP 500–1000 mg/kg feed Novartis Ltd. Ranamox Amoxicillin trihydrate 300–400 mg/kg feed Renata Ltd. Renaflox Ciprofloxacin hydrochloride 500 mg/1–1.5 L water Renata Ltd. Renamycin Oxytetracycline 300–420 mg/kg feed Renata Ltd. Renatrim Sulfadiazine, trimethoprim 3–5 mL/kg feed for 3–5 days Renata Ltd. Otetra-vet 20% Oxytetracycline 5 gm/kg feed Square Pharmaceuticals Ltd. Biomycin Oxytetracycline 5 gm/kg feed Biopharma Ltd. Aquamycine Oxytetracycline 5 gm/kg feed ACI Animal Health Ltd. EST-Vet Erythromycin thiocyanate, sulphadiazine, trimethoprim 3–5 gm/kg feed Eon Animal Health Ltd. Cotrim-vet Sulphamethoxazole, trimethoprim 5 gm/kg feed Square Pharmaceuticals Ltd. Sulprim-vet Sulphadyazine, trimethoprim 3–5 gm/kg feed Square Pharmaceuticals Ltd. AT-vet Sulphadyazine, trimethoprim 3–5 gm/kg feed ACME Laboratories Ltd Erisen-vet Erythromycin, sulphadiazine, trimethoprim 5 gm/kg feed Square Pharmaceuticals Ltd. Ciprocin-Vet Ciprofloxacin 5 ml/kg feed Square Pharmaceuticals Ltd. Turbonid Erythromycin, sulphadiazine, trimethoprim 5 gm/kg feed Eskayef Pharmaceuticals Ltd. Renaquine Flumequine 20% 3–5 ml/kg feed Renata Ltd. Levomax Levofloxacin 10% 5 ml/kg feed Eskayef Pharmaceuticals Ltd. Maxtor Chlortetracycline 45% 5 gm/kg feed Eskayef Pharmaceuticals Ltd. Eska'CTC Chlortetracycline 20% 5 gm/kg feed Eskayef Pharmaceuticals Ltd. Enroflox DS Enrofloxacin BP 20% 3–5 ml/kg feed Eskayef Pharmaceuticals Ltd. Augment vet Amoxicillin trihydrate BP & clavulanate BP 5 gm/kg feed Eskayef Pharmaceuticals Ltd. Bactitap Oxytetracycline hydrochloride 5 gm/kg feed ACI Animal Health Ltd. Eryvet Erythromycin sulphadiazine 5 gm/kg feed ACI Animal Health Ltd. FRA C12 1-Monolaurin & essential oil 5 ml/kg feed ACI Animal Health Ltd. Ciprovet Ciprofloxacin 10% 5 ml/kg feed Eon Animal Health Product Ltd. Eon CTC Chlortetracycline 20% 5 gm/kg feed Eon Animal Health Product Ltd. CF-vet-20 Ciprofloxacin 5 gm/kg feed Prapti Animal Health Novoflor Florfenicol 1–2 ml/kg feed Eskayef Pharmaceuticals Ltd. Cidaflox Ciprofloxacin 5 ml/kg feed Opsonin Pharmaceuticals Ltd. Flumequine Flumequine BP 20% 5 ml/kg feed Eon Animal Health Product Ltd. Aquamysine Chlortetracycline 1-1.5 kg/ton feed Fishtech BD Amoxifish Amoxicillin trihydrate 3–5 g/ kg feed Fishtech BD Bactitab Oxytetracycline 20% 5 g/kg body weight for 5–7 days ACI Animal Health Ltd. Acimox (vet) Powder Amoxicillin trihydrate 1 g/1 kg feed ACI Animal Health Ltd. Oxysentin 20% Oxytetracycline HCl BP 100–200 g/100 kg feed for 5–7 days Novartis Ltd. Chlorsteclin Chlorotetracycline 200–300 g/100 kg feed Novartis Orgamycins 15% Oxytetracycline HCl BP 60 g/100 kg for 10 days Organic Pharma Orgacycline 15% Chlortetracycline 200–300 g/100 kg feed (5–7 days) Organic Pharma Oxin WS Oxytetracycline 20% 50 g/kg body weight Navana Pharma Ltd. Otetravetpowder 50 Oxytetracycline 11–16 g/100 kg body weight Square Pharmaceuticals Ltd Sulphatrim Sulphadiazine 50g/kg body weight,5–7 days Square Pharmaceuticals Ltd. Environmental monitoring studies indicate widespread antibiotic contamination in aquaculture-associated surface waters in Bangladesh. Salma et al. ( 2025 ) detected 26 antibiotics from seven classes, with sulfadiazine, sulfamethoxazole, trimethoprim, erythromycin-H₂O, and amoxicillin occurring most frequently; sulfadiazine reached concentrations up to 25,000 ng L⁻¹, particularly in striped catfish ( Pangasianodon hypophthalmus ) ponds. Several compounds posed a high ecological risk and exerted strong selective pressure on antimicrobial resistance. Consistently, Faruk et al. ( 2021 ) reported intensive antibiotic use in aquaculture farms of the Mymensingh region, where Oxytetracycline and amoxicillin were the most commonly used, followed by ciprofloxacin and sulfadiazine, supplied mainly by major national pharmaceutical companies. Across regions, antibiotic selection and dosing in aquaculture are largely guided by farmers’ personal experience, package instructions, and advice from chemical vendors, reflecting limited knowledge of antibiotic modes of action and the absence of prescription-based regulation. Salma et al. ( 2022 ) reported that in the Rajshahi district of Bangladesh, 88% of fish farmers lacked expertise regarding aqua-chemical and antibiotic use, while 81% were unaware of appropriate dosages. Limited access to diagnostic infrastructure further promotes the empirical use of antibiotics, particularly among small-scale farmers (Chowdhury et al., 2022 ). Such non-judicious use accelerates the emergence and spread of antimicrobial resistance and disrupts aquatic microbial communities, posing risks to animal, public, and ecosystem health and sustainability (Chowdhury et al., 2022 ). 4. AMR in Aquaculture Systems of Bangladesh Antimicrobial-resistant bacteria are widely detected across the interconnected domains of the environment, animals, and humans, underscoring the importance of a One Health perspective for understanding the emergence and dissemination of resistance (Robinson et al., 2016 ). Bacteria can pump antibiotics out of the cell, modify drug target sites, or enzymatically degrade antibiotics. They may also alter cell wall permeability to prevent drug entry. Additionally, resistance genes can spread through horizontal gene transfer, enhancing bacterial survival (Fig. 1 ). A comprehensive understanding of AMR evolution and transmission dynamics across this triad is essential for anticipating emerging pathogens and designing effective mitigation strategies. Prolonged and often unregulated antibiotic use in aquaculture systems can accelerate the development of resistance in both farmed fish and associated bacterial communities and may contribute to its dissemination into surrounding ecosystems (Cabello et al., 2016 ; Woźniacka et al., 2025 ). Important bacterial genera associated with aquaculture environments include Aeromonas (e.g., A. hydrophila ), Vibrio (e.g., V. parahaemolyticus ), Staphylococcus (e.g., S. aureus ), Pseudomonas (e.g., P. aeruginosa ), Salmonella spp., and Escherichia coli , some of which are recognized as opportunistic or zoonotic pathogens of public health concern (Boss et al., 2016 ; He et al., 2016; Budiati et al., 2013 ; Kitiyodom et al., 2010 ). In Bangladesh, inadequate regulation and widespread use of antibiotics in aquaculture pose significant risks to aquatic animal health, environmental integrity, and public health (Salma et al., 2022 ). Several studies have documented extensive antimicrobial resistance among bacterial isolates recovered from cultured fish in Bangladesh. Hossain et al. ( 2018 ) identified 58 bacterial isolates belonging to nine genera from fish samples, with Klebsiella spp., Pseudomonas spp., Staphylococcus aureus , Vibrio spp., and E. coli being most prevalent. Alarmingly, all isolates exhibited complete resistance (100%) to tetracyclines, penicillins, cephalosporins, aminoglycosides, and macrolides, while resistance rates of approximately 80% were reported for sulfonamides and fluoroquinolones. Pathogen-specific investigations further highlight the severity of AMR in Bangladeshi aquaculture. Siddique et al. ( 2021 ) reported a high prevalence of Vibrio parahaemolyticus in aquaculture farms of Satkhira, coastal Bangladesh, isolated from water, sediment, tilapia, rui, and shrimp. The occurrence of this pathogen was positively correlated with elevated temperature and salinity. Several isolates harbored the virulence gene trh , indicating potential pathogenicity. These isolates were further confirmed using molecular (PCR) and phenotypic identification methods, with exceptionally high resistance (94.1%) to ampicillin and amoxicillin. Genetic analyses revealed diverse yet related resistant strains, indicating a substantial public health and aquaculture disease risk in the region. Similarly, Foysal et al. ( 2011 ) isolated Pseudomonas fluorescens from carp and catfish exhibiting hemorrhagic septicemia, indicating its possible role as an associated or opportunistic pathogen, and evaluated its antibiotic susceptibility profile. While isolates remained sensitive to streptomycin and gentamicin, resistance to chloramphenicol was widespread, and approximately 80% of isolates exhibited multidrug resistance (MDR). Khan et al. ( 2022 ) assessed bacterial isolates from shrimp farms in Bagerhat district and reported that 78.0% were resistant to at least one antibiotic, and 29.3% were MDR to commonly used antibiotics, including ampicillin, oxytetracycline, ciprofloxacin, and azithromycin. Studies focusing on shrimp culture systems further confirm the persistence of resistant Vibrio species. Hossain et al. ( 2012 ) detected Vibrio spp. in shrimp pond water and harvested black tiger shrimp ( Penaeus monodon ), with higher contamination levels observed in market samples compared to farm-level samples. Antibiotic susceptibility testing revealed the highest resistance to penicillin and cephalexin (28.57%), and MDR was detected in at least one isolate. The authors suggested these patterns to indiscriminate antibiotic use during culture and post-harvest contamination during handling and marketing. In the Khulna region, Haque et al. ( 2023 ) reported Vibrio spp. in 34% of shrimp farming–associated samples, with significantly higher prevalence in shrimp (54%) than in mud (26%) or water (22%). Dominant species included Vibrio cholerae , V. parahaemolyticus , and V. alginolyticus , with resistance rates ranging from 15.7% to 92.2% against ampicillin, amikacin, cefotaxime, tetracycline, ceftazidime, gentamicin, nalidixic acid, levofoxacin, and ciprofoxacin. Notably, more than half (52.9%) of the isolates were multidrug-resistant, highlighting a critical food safety concern. Recent evidence suggests that AMR is also highly prevalent in freshwater aquaculture systems. Sultana et al. ( 2025 ) reported an exceptionally high occurrence of V. cholerae and V. parahaemolyticus in tilapia and rui cultured in Bangladesh, as well as in fish scales, gut samples, and tank water. V. cholerae was detected in 100% of tilapia and 92.3% of rui samples, while V. parahaemolyticus was present in over 92% of both species. Antibiotic susceptibility assays showed moderate resistance to aztreonam and ciprofloxacin, but high sensitivity to gentamicin and ceftriaxone. Multidrug resistance was observed in 12% of V. cholerae and 37.5% of V. parahaemolyticus isolates, and a small proportion of V. parahaemolyticus exhibited extreme drug resistance. Beyond bacterial isolates, the presence of antibiotic residues in fish tissues and aquatic environments further is consistent with ongoing exposure and selective pressure. Nayem et al. ( 2025 ) detected residues of ciprofloxacin, oxytetracycline, chlortetracycline, levofloxacin, and enrofloxacin in commercially farmed fish species, including tilapia, stinging catfish, climbing perch, and pabda, using TLC and UHPLC techniques. Although hazard quotient values were below unity, suggesting no immediate toxic risk, the persistence of residues raises concerns regarding chronic exposure and AMR development. Consistent with these findings, antibiotics such as sulfamethoxazole, trimethoprim, tylosin, sulfadiazine, and amoxicillin have been detected at ng L⁻¹ concentrations in surface waters of freshwater finfish and brackish-water shellfish farms, with higher detection frequencies in finfish systems (Hossain et al., 2017 ). While preliminary ecological and resistance risk assessments indicated risk quotients below one, the widespread occurrence of antibiotics in farm waters highlights continuous environmental exposure and reinforces the need for improved antibiotic stewardship, surveillance, and wastewater management in aquaculture. Taken together, the widespread occurrence of antimicrobial-resistant pathogens and antibiotic residues in Bangladeshi aquaculture underscores the limitations of antibiotic-dependent disease management. These findings highlight the urgent need to transition to effective non-antibiotic alternatives that can reduce disease burden without exacerbating selection pressures for resistance. Sustainable approaches such as probiotics, prebiotics, immunostimulants, phytobiotics, vaccines, and emerging technologies therefore represent promising options for future aquaculture health management strategies. Evaluating the feasibility and applicability of these alternatives is essential for ensuring long-term productivity, environmental safety, and public health protection. 5. Alternative Therapies for Controlling Fish Diseases in Aquaculture Numerous alternative disease management strategies have been developed worldwide to overcome the limitations associated with conventional antibiotic use in aquaculture, including the emergence of AMR, accumulation of drug residues in aquatic products and environments, and increasing regulatory restrictions on antibiotic application. These approaches aim to control infectious diseases while minimizing the selection for antibiotic resistance and reducing residue-related risks. Key alternatives include probiotics, prebiotics, synbiotics, immunostimulants, vaccination, quorum-quenching agents, antimicrobial peptides, biosurfactants, bacteriocins, and nanotechnology-based interventions (Fig. 2 ). Many of these strategies function by enhancing host immunity, modulating gut microbiota, disrupting pathogen virulence mechanisms, or preventing pathogen colonization rather than directly killing microorganisms. While several alternatives, such as probiotics, limited commercial use of nanoparticles, and vaccines in some species, including Oreochromis niloticus, Cyprinus carpio , Oncorhynchus mykiss , and Lates calcarifer , are already applied in commercial aquaculture systems worldwide, others, including quorum-quenching compounds, bacteriophages, and antimicrobial peptides are still being evaluated for effective large-scale application (Rahman et al. 2022 ; Kim et al. 2023 ; Ibrahim et al. 2021 ; Aly et al. 2023 ; Musthafa et al. 2018 ). The effectiveness and adoption of these alternatives vary depending on species, culture systems, environmental conditions, and management practices. In parallel, the development of accurate and rapid disease diagnostic technologies is increasingly recognized as a critical component of sustainable aquaculture health management, as it enables timely pathogen identification, supports the targeted application of alternatives such as vaccines, probiotics, and antimicrobial peptides, and reduces the reliance on empirical antibiotic treatments. Early and precise pathogen detection enables timely intervention, reduces unnecessary antibiotic use, and supports the application of targeted, non-antibiotic therapies. 5.1.1 Vaccines Vaccination is widely recognized as one of the most effective approaches for preventing a broad spectrum of bacterial and viral diseases in aquaculture and contributes substantially to the environmental, social, and economic sustainability of fish farming systems. An ideal fish vaccine is expected to elicit a specific and long-lasting immune response while providing robust protection against target pathogens (Muñoz-Atienza, 2021). Globally, fish are vaccinated annually, and in several aquaculture-intensive regions, disease management strategies have progressively shifted from antibiotic dependence toward vaccination-based control (Ma et al., 2019 ). The introduction of vaccines has led to a dramatic reduction in antibiotic use in fish farming, establishing vaccination as a cost-effective and sustainable method for controlling infectious diseases in aquaculture. Advances in molecular biology and improved understanding of protective antigens have accelerated the development of next-generation vaccines for both animal and human health applications (Brun et al., 2011 ; Kim et al., 2016 ; Frietze et al., 2016 ). Consequently, countries such as China, Japan, and Norway have successfully integrated vaccination programs into their aquaculture practices, highlighting global recognition of vaccines as essential tools for effective health management (Gudding and Van Muiswinkel, 2013 ). Currently, a wide range of vaccine types are available for aquaculture, including DNA vaccines, recombinant vaccines, and conventionally produced formulations, many of which have been approved for use in specific fish species (Table 3 ). Based on preparation methods, aquaculture vaccines are commonly classified as live attenuated, inactivated (killed), subunit, and vectored vaccines. Conventional vaccines, particularly live attenuated and inactivated formulations, remain widely used due to their proven ability to induce strong and specific immune responses in fish. At the same time, molecular and recombinant vaccine technologies offer more targeted, safer, and adaptable approaches, representing promising advances in sustainable disease-prevention strategies for modern aquaculture systems (Mondal and Thomas, 2022 ). Table 3 Vaccination strategies targeting key pathogens in aquaculture species Vaccine type Target pathogen Host species Delivery method Efficacy (%) References Live Attenuated Edwardsiella ictaluri Channel catfish ( Ictalurus punctatus ) Immersion 88 Abdelhamed et al. 2018 Polyvalent Streptococcosis, Lactococcosis, and Enterococcosis Tilapia ( Oreochromis niloticus ) I/P and Immersion 60 Abu-Elala et al. 2019 Bivalent Listonella anguillarum Juvenile sea bass ( Dicentrarchus labrax ) Immersion 92–100 Angelidis et al. 2006 DNA vaccine Koi herpesvirus Common carp Cyprinus carpio Immersion 63 Aonullah et al. 2017 Bivalent Vibrio vulnificus Freshwater eel Oral, I/P and Immersion 80 Esteve-Gassent et al., 2004 PLGA encapsulated inactivated (killed) Viral haemorrhagic septicaemia virus (VHSV) Olive flounder ( Paralichthys olivaceus ) Immersion and oral 60–73 Kole et al. 2019 Inactivated VHSV Olive flounder (P. olivaceus) Immersion 72–89 Hwang et al. 2017 Inactivated V. anguillarum Turbot ( Scophthalmus maximus ) Immersion 59–81 Wang et al. 2016 Inactivated recombinant Francisella noatunensis Nile tilapia ( O. niloticus ) I/P 82 Shahin et al. 2019 Formalin-killed vaccine Streptococcus , Enterococcus , and Lactococcus Nile tilapia ( O. niloticus ) I/P) and bath immersion 60–88 Akter et al., 2022 Bivalent Aeromonas sp. Catfishes ( Heteropneustes fossilis , Clarias batrachus , and Pangasius pangasius ) IM and oral routes 88–93 Rahman et al. 2022 Recombinant subunit White spot syndrome virus (WSSV) Shrimp ( L. vannamei ) Oral administration 80 Kim et al., 2023 Recombinant WSSV Shrimp Oral administration 70 Lanh et al., 2021 Inactivated V. anguillarum Rainbow trout ( O. mykiss ) I/P 100 Lim et al. 2023 Live vaccine V. anguillarum Tiger puffer ( Takifugu rubripes) IM 80–90 Liu et al. 2018 Inactivated whole-cell bivalents V. alginolyticus and S. agalactiae Tilapia I/P 70–90 Abotaleb et al. 2023 Inactivated F. columnare Red tilapia ( Oreochromis sp.) Immersion 60 Kitiyodom et al. 2019 Inactivated V. vulnificus Turbot ( Scophthalmus maximus ) I/M 53–63 Gu et al. 2021 Live I. multifiliis Channel catfish ( Ictalurus punctatus ) I/P N/A Xu et al. 2020 DNA Tilapia lake virus Nile tilapia IM 85 Yu et al. 2022 In Bangladesh, vaccination against streptococcosis has been experimentally evaluated but remains limited evidence of routine farm-level adoption. Akter et al. ( 2022 ) demonstrated that a whole-cell formalin-killed Enterococcus vaccine administered to Nile tilapia via intraperitoneal injection and bath immersion significantly enhanced immune responses (RBC, WBC, and IgM levels) and reduced mortality following challenge, with relative percent survival reaching up to 88.6% and 69.1%, respectively. Rahman et al. ( 2022 ) also reported that a bivalent inactivated vaccine prepared from Aeromonas hydrophila and A. veronii , administered via intramuscular and oral routes to brood fish, significantly enhanced hematological parameters and IgM antibody levels in brood fish, larvae, and eggs. Vaccinated groups showed markedly higher relative percent survival (RPS) in larvae of shing, magur, and pangas (exceeding 88–93%) following pathogen challenge compared to non-vaccinated controls. Despite demonstrating strong protective efficacy and transgenerational immune benefits under controlled conditions, such vaccination strategies remain largely confined to experimental settings and have not been effectively scaled up for routine farm-level implementation in Bangladesh. Despite the proven effectiveness of vaccination in aquaculture, its adoption in Bangladesh remains limited due to several structural and operational constraints. These include the absence of locally produced, species-specific vaccines, limited cold-chain infrastructure, and high costs associated with vaccine procurement and delivery. Moreover, the lack of licensed commercial fish vaccines and the limited availability of commercial suppliers in the domestic market have further constrained large-scale implementation. Additionally, the predominance of small-scale and extensive farming systems complicates mass vaccination, particularly for injectable vaccines. Inadequate diagnostic capacity and limited awareness among farmers regarding vaccine benefits further restrict uptake. Lack of coordinated national vaccination programs also hinders widespread implementation. Addressing these barriers through targeted research, capacity building, and policy support is essential for integrating vaccination into sustainable aquaculture health management in Bangladesh. 5.1.2 Probiotics Probiotics are defined as live microorganisms which, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO, 2002). They are widely used worldwide as dietary supplements in food and feed formulations and commonly include bacterial genera such as Bacillus spp., Lactobacillus , and Bifidobacterium , as well as certain yeast strains (Bondad-Reantaso et al., 2023 ). In aquaculture, probiotics play an important role in enhancing nutrition, improving feed utilization, strengthening immune responses, and increasing resistance to infectious diseases (Rahayu et al., 2024 ) (Table 4 ). Unlike antibiotics, which act primarily through bactericidal or bacteriostatic mechanisms but can also disrupt host-associated microbiota and ecological balance, probiotics exert their beneficial effects through multiple biological pathways, including competitive exclusion of pathogens, modulation of host immune responses, enhancement of digestive processes, and stabilization of microbial communities. These include competitive exclusion of pathogenic microorganisms, inhibition of pathogen adhesion and colonization, production of antimicrobial compounds such as bacteriocins, enhancement of intestinal barrier integrity, reduction of intestinal pH, and modulation of host immune responses (Williams et al., 2010). Extensive research has demonstrated that probiotic supplementation can significantly improve growth performance, feed conversion efficiency, immune competence, and overall health status of cultured aquatic species, while also contributing to improved water quality in farming systems (Tabassum et al., 2021 ). Although antibiotics have historically played a key role in controlling bacterial diseases in aquaculture, their widespread and often unregulated use has contributed to antimicrobial resistance, residue accumulation, and ecological imbalances within cultured systems (Mahmud & Haque, 2025 ). In response, probiotics are increasingly promoted as safer and more sustainable disease-management alternatives. Experimental evidence suggests the effectiveness of probiotics in disease prevention. Taoka et al. ( 2006 ) demonstrated that feeding viable probiotics to Oreochromis niloticus significantly enhanced non-specific immune responses, including lysozyme activity, neutrophil migration, and bactericidal activity, thereby increasing resistance against Edwardsiella tarda . Probiotics have also been shown to synthesize essential nutrients, such as polyunsaturated fatty acids and vitamin B₁₂, contributing to host nutrition regardless of their localization within the gut, water column, or sediment (Eichmiller et al., 2016 ; Yoshida et al., 2016 ). Recent studies further highlight species- and strain-specific probiotic effects. Shija et al. ( 2024 ) reported that dietary supplementation with Bacillus amyloliquefaciens AV5 for 30 days significantly increased lysozyme levels in both serum and skin mucus of Nile tilapia compared to control groups. Similarly, Nikoskelainen et al. ( 2001 ) observed reduced mortality in fish fed diets containing Lactobacillus rhamnosus following challenge with virulent Aeromonas salmonicida . Optimal probiotic inclusion levels, typically ranging from 10⁴ to 10⁸ CFU g⁻¹ of feed, have been shown to stimulate respiratory burst activity, thereby enhancing disease resistance (Nayak, 2010 ). In addition, Phaeobacter inhibens , known for producing the antimicrobial compound tropodithietic acid (TDA), has demonstrated strong inhibitory effects against the larval pathogen Vibrio anguillarum in copepods, highlighting its potential application as a probiotic in live feed systems. Al-Dohail et al. ( 2011 ) further demonstrated that dietary supplementation with Lactobacillus acidophilus significantly improved haematological and biochemical parameters, liver and kidney health, and resistance to Staphylococcus xylosus , Aeromonas hydrophila , and Streptococcus agalactiae in African catfish ( Clarias gariepinus ). Collectively, these findings indicate that probiotics are effective biocontrol agents and sustainable tools for disease management in modern aquaculture. Table 4 Overview of probiotics used in disease management in aquaculture Probiotic Strain Host species Pathogen Duration Reported effects References Lacticaseibacillus rhamnosus FS3051, Limosilactobacillus reuteri FS3052, and Bacillus subtilis natto NTU-18 Grey mullet ( Mugil cephalus ) Nocardia seriolae 28 days Immune gene expression was enhanced, while reducing Mycoplasma and Rhodobacter, which were negatively correlated with immune responses Chan et al. 2024 Carnobacterium maltaromaticum B26 and Carnobacterium divergens B33 Rainbow trout ( Oncorhynchus mykiss ) A. salmonicida and Yersinia ruckeri. 3 weeks Enhanced both cellular and humoral immune responses, increased respiratory burst activity, and elevated lysozyme levels in serum and gut mucosa. Kim and Austin, 2006 Kocuria SM1 and Rhodococcus SM2 Rainbow trout ( O. mykiss ) V. anguillarum N/A Enhanced innate immune responses through increased activity of cell wall proteins and whole cell proteins, leading to elevated bacterial killing activity, leukocyte counts, and immunoglobulin levels. Sharifuzzaman et al. 2011 Roseobacter 27 − 4 Turbot ( Scophthalmus maximus ) larvae V. anguillarum 10 days Protected against V. anguillarum infection Planas et al., 2006 Lactobacillus sakei BK19 Oplegnathus fasciatus E. tarda 6 weeks Increase innate immunity levels and Serum complement and antiprotease activities. Altered hematological parameters. Harikrishnan et al., 2011 Lactobacillus pentosus PL11 Japanese eel Anguilla japonica E. tarda 5 weeks Plasma immunoglobulin M levels, CAT and SOD activities, Hematological parameters, and mieloperoxidase were significantly higher, improving health performance. Lee et al. 2013 Lactococcus lactis BFE920 Olive flounder ( Paralichthys olivaceus ) Streptococcus iniae 2 weeks Innate immunity activated by the L. lactis administration: increased lysosomal activity, disease resistance against pathogens. Kim et al. 2013 lactic acid bacterium Pediococcus pentosaceus strain 4012 (LAB4012) Groupers ( Epinephelus spp.) V. anguillarum N/A Leukocyte abundance in peripheral blood and the phagocytic activity of head-kidney phagocytes were altered, indicating modulation of the immune response. Huang et al., 2014 Enterococcus casseliflavus Rainbow trout Oncorhynchus mykiss S. iniae 8 Weeks Significantly improved gut health, innate immunity, and disease resistance, as reflected by increased serum protein, albumin, IgM, leukocyte counts, and neutrophil levels. Safari et al.2016 Enterococcus gallinarum Sea bass V. anguilarum N/A Produced a moderated protective effect against V. anguillarum infection. Sorroza et al., 2013 Lc. lactis BFE920 and Lb. plantarum FGL0001 Olive flounder S. iniae 30 days Enhanced skin mucus lysozyme activity and the phagocytic activity of innate immune cells, indicating a clear immunostimulatory effect. Beck et al. 2015 Saccharomyces cerevisiae Nile tilapia, (O. niloticus) A. hydrophila 12 weeks The lowest fish mortality and bacterial counts were obtained. Abdel-Tawwab et al. 2008 Streptomyces strains CLS-28, CLS-39, CLS-45 Penaeus monodon Vibrio harveyi and V. proteolyticus 15 days Higher survival compared to the control against the pathogen. Das et al. 2010 B. subtilis Shrimp ( Litopenaeus vannamei ) Vibrio harveyi 8 weeks All immune-related genes were significantly up-regulated, resulting in disease resistance through an enhanced immune response in shrimp. Zokaeifar et al. 2012 Bacillus subtilis Hybrid grouper (Epinephelus fuscoguttatus× E. lanceolatus V. harveyi 42 days Decreased the expression of both inflammation and apoptosis-related genes, modulating immunity. Han et al. 2024 Lactobacillus plantarum Litopenaeus vannamei V. alginolyticus 56 days Total hemocyte count increased, indicating improved immunity and disease resistance, without adverse effects on growth performance or hepatopancreas morphology. Lee et al. 2024 B. subtilis and Lactobacillus spp. Labeo rohita A. veronii 90 days Probiotic-treated fish exhibited significantly enhanced gut immunological parameters, improved hepatic cellular organization with more regular nuclei and reduced intercellular spaces, and the highest post-challenge survival rate. Ferdous et al. 2024 Lactobacillus plantarum Oncorhynchus mykiss A. hydrophila 60 days Increases in RBC, hemoglobin (Hb), MCH, MCHC, and MCV were observed, accompanied by enhanced resistance against A. hydrophila . Soltani et al. 2019 Lactobacillus casei Cyprinus carpio A. hydrophila 75 days Intestinal enzyme activities, including ALP, lipase, amylase, trypsin, and protease, were significantly elevated. Mohammadian et al. 2019 B. subtilis L. plantarum P. aeruginosa Labeo rohita A. hydrophila 60 days Serum lysozyme activity, as well as phagocytic and respiratory burst activities in head kidney macrophages of L. rohita , increased significantly. Giri et al. 2014 In Bangladesh, probiotics are used in aquaculture; however, their application is primarily oriented toward growth promotion and feed efficiency rather than as deliberate alternatives to antibiotics or other antimicrobial agents. Commercial probiotic products are widely available and are commonly used to improve water quality, enhance digestion, and accelerate growth performance in cultured fish and shrimp. Despite growing awareness of antimicrobial resistance, probiotics are limited evidence of using in a targeted manner for disease prevention or pathogen control at the farm level. Several laboratory- and hatchery-based studies conducted in Bangladesh have demonstrated the efficacy of probiotics against important bacterial pathogens, including Aeromonas , Vibrio , and Streptococcus species. These studies reported enhanced immune responses, reduced mortality, and improved resistance under controlled experimental conditions (Ferdous et al. 2024 ; Hossain et al. 2022 ). However, large-scale field validation and systematic farm-level application remain limited. Constraints such as inconsistent product quality, lack of strain-specific recommendations, limited farmer knowledge, and absence of regulatory guidelines hinder the wider adoption of probiotics as true antimicrobial alternatives (Hossain et al., 2023). Consequently, although probiotics are increasingly used for growth promotion and water quality improvement, their specific application as a disease-prevention strategy to reduce antibiotic dependency in Bangladeshi aquaculture remains underutilized. 5.1.3 Prebiotics and Synbiotics Prebiotics are defined as non-digestible substrates that beneficially influence the host by selectively stimulating the growth and activity of health-promoting microorganisms in the gastrointestinal tract (Lordan et al., 2020 ; Srirengaraj et al., 2023 ). Commonly used prebiotic compounds in aquaculture include mannan oligosaccharides (MOS), fructooligosaccharides (FOS), arabinooligosaccharides (AOS), β-glucans, inulin, chitosan and other functional polysaccharides, which are recognized for their roles in enhancing innate immunity, gut health, and disease resistance in aquatic organisms (Geraylou et al., 2013 ; Khanjani et al., 2022 ) (Table 5 ). Among these, MOS is one of the commonly used prebiotics in animal and fish diets, owing to its capacity to improve growth performance, feed utilization, survival rates, immune responses, and antagonistic activity against aquatic pathogens (Mustafa et al., 2020 ; Xue et al., 2022 ). Several studies have demonstrated that prebiotics exert their beneficial effects primarily by modulating gut microbiota composition, stimulating immune function, and enhancing resistance to infectious diseases in both finfish and shellfish. For instance, an effective prebiotic is characterized by resistance to host digestive enzymes, lack of absorption in the foregut, fermentability by gut microbiota, and selective stimulation of beneficial bacterial populations, ultimately leading to improved host health and physiological condition (Goh et al., 2022 ). Experimental evidence further supports the stress-mitigating and immunoprotective roles of prebiotics. Xue et al. ( 2022 ) demonstrated that dietary MOS significantly enhanced growth performance, digestive enzyme activity, antioxidant capacity, and innate immune responses in common carp under ammonia stress, while also reducing liver, gill, and intestinal tissue damage. Similarly, Mustafa et al. ( 2020 ) reported that dietary FOS significantly altered the gut microbial community structure of Pacific white shrimp ( Litopenaeus vannamei ), highlighting the capacity of prebiotics to modulate intestinal microbiota, although growth and immune responses were not significantly affected during short-term feeding trials. Synbiotics, defined as synergistic combinations of probiotics and prebiotics, have gained increasing attention due to their combined capacity to enhance gut microbial balance and host immunity more effectively than either component alone (Hardi et al., 2022 ). Ye et al. ( 2011 ) demonstrated that synbiotic diets containing FOS, MOS, and Bacillus clausii significantly improved growth performance, digestive enzyme activity, lysozyme-mediated immunity, and lipid metabolism in Japanese flounder, resulting in superior health outcomes compared with single probiotic or prebiotic treatments. Likewise, Pawar et al. ( 2023 ) showed that synbiotic supplementation in feed (0.5% FOS + 10⁶ CFU g⁻¹ Bacillus subtilis ) markedly enhanced immune responses and post-challenge survival of Labeo fimbriatus fingerlings against Aeromonas hydrophila . In Bangladesh, recent studies suggest the potential relevance of prebiotics and synbiotics as sustainable alternatives to antibiotics in aquaculture. Munni et al. ( 2023 ) demonstrated that dietary supplementation with prebiotics and synbiotics significantly improved growth performance, feed efficiency, and immune indicators in Nile tilapia compared with antibiotic-treated groups, with synbiotics yielding the highest body weight and white blood cell counts without inducing pathological liver alterations. Similarly, Linda et al. ( 2025 ) reported that synbiotic supplementation enhanced intestinal health, hematological parameters, and liver histology in Asian stinging catfish ( Heteropneustes fossilis ), conferring greater host resilience and reduced disease susceptibility. Table 5 Overview of Prebiotics and Synbiotics used in aquaculture health management Prebiotics/mixtures & Synbiotics Host species Mode of application Duration Reported effects References FOS, GOS, MOS Red drum (Sciaenops ocellatus) 10 g/kg diet 56 days Intestinal enzyme activities, including ALP, lipase, amylase, trypsin, and protease, were significantly elevated. Zhou et al. 2010 Inulin, GOS, soybean oligosaccharide (SBO) Sex reversed red hybrid tilapia 5% of diet 60 days Fish fed the diet containing 5% GOS exhibited the lowest post-challenge mortality rate. Plongbunjong et al. 2011 β-glucan, MOS Common carp ( C. carpio ) 0.5–2.5 g/kg diet 8 weeks Improve the feed efficiency and growth performance of C. carpio fingerlings as well as their resistance to A. hydrophila infection. Ebrahim et al. 2012 β-glucan, GOS, MOS Snakehead ( Channa striata ) β-glucan (2 g/kg diet), GOS (5 g/kg diet), MOS (5 g/kg diet) 16 weeks The treatment proved optimal for growth performance and enhanced the expression of immune regulatory genes in Channa striata . Munir et al. 2016 β-glucan, MOS Caspian trout ( Salmo trutta caspius) MOS (4 g/kg diet) +β-glucan (4 g/kg diet) 8 weeks Humoral innate immunity was enhanced, accompanied by reduced transcription of inflammation-related genes. Jami et al. 2019 β-glucan, MOS Shabout ( Tor grypus ) 0.5, 1, and 1.5% 90 days At a 1.5% inclusion level, the diet positively influenced growth performance, carcass protein content, intestinal microflora, and immune responses of shabout. Mohammadian et al. 2021 β-glucan, MOS Atlantic cod ( Gadus morhua ) 1 g/kg diet 5 weeks Both mannan oligosaccharides and β-glucans enhanced Atlantic cod's ability to respond to V. anguillarum infection. Lokesh et al. 2012 MOS B. subtilis Nile tilapia ( O. niloticus ) 1 g /kg − 1 6 weeks The combined treatment positively influenced intestinal morphometry and carcass composition in Nile tilapia. Azevedo et al. 2016 β-glucan Aspergillus oryzae (ASP) Nile tilapia ( O.niloticus ) 0.5/ 1 g kg − 1 60 days Enhanced immune responses in tilapia, with pronounced modulation of hematocrit, hemoglobin, RBC, WBC, total protein, and digestive enzyme activities, reaching peak levels in the synbiotic-treated group. Dawood et al. 2020 MOS & Bacillus subtilis Indian Major Carp ( Cirrhinus mrigala ) N/A 60 days Enhancing innate immunity and disease resistance of C. mrigala against A. hydrophila infection. Kumar et al. 2018 GOS & Pediococcus acidilactici Common carp ( C. carpio ) GOS 10 g kg − 1 + P. acidilactici 1 g kg − 1 [0.9 × 107 CFU] lyophilized 8 weeks, Exerted positive effects on selected mucosal and serum immune parameters. Modanloo et al. 2017 GOS B. subtilis L. rohita GOS 1 g kg − 1 + B. subtilis 1 g kg − 1 8 weeks, Elicited earlier antioxidant activation, enhanced innate and adaptive immune responses, modulation of immune-related cytokine gene expression, and improved disease resistance. Devi et al. 2019 Recent studies further reinforce the disease-mitigating potential of synbiotics under Bangladeshi aquaculture conditions. Islam et al. ( 2025 ) demonstrated that dietary synbiotics significantly improved growth performance, gut morphology, liver health, and muscle development in Gangetic mystus ( Mystus cavasius ), with an optimal inclusion level. Importantly, synbiotic-fed fish exhibited elevated red and white blood cell counts, increased neutrophil and lymphocyte populations, and complete survival following challenge with Aeromonas veronii , underscoring their strong immunoprotective capacity and suitability as antibiotic-free disease management tools. Overall, prebiotics and synbiotics represent promising functional feed additives for promoting gut health, immune competence, and disease resistance in aquaculture species. While laboratory and controlled feeding trials in Bangladesh demonstrate clear benefits, however, evidence of large-scale adoption at the farm level remains limited. Future research should prioritize long-term field validation, cost–benefit analyses, and species-specific optimization to facilitate the broader integration of prebiotic and synbiotic strategies into sustainable aquaculture health management systems in Bangladesh. 5.1.4 Nanoparticles Nanoparticles (NPs) possess unique physicochemical properties due to their nanoscale size and high surface-area-to-volume ratio, enabling enhanced antimicrobial activity and targeted applications in aquaculture, including feed-based delivery systems, water disinfection, and antimicrobial surface coatings in culture facilities. One of the primary antimicrobial mechanisms of NPs involves direct disruption of bacterial cell membranes. Because bacterial cell surfaces are typically negatively charged, nanoparticles, particularly those with cationic properties, can electrostatically bind to the cell wall depending on surface chemistry and water matrix, destabilizing the membrane, increasing permeability, and ultimately causing cell lysis. Certain nanoparticles, such as graphene oxide, exert physical membrane damage of bacterial, whereas others, including silver nanoparticles (AgNPs), chemically alter membrane integrity through ion release and oxidative stress (Mahmud and Haque, 2025 ). These mechanisms are effective against both Gram-positive and Gram-negative bacteria and are less prone to resistance development, as they do not rely on specific biochemical targets (Wang et al., 2017 ; Godoy et al., 2021). Recent studies suggest that nanoparticles could play a promising role in aquaculture disease management by complementing or enhancing conventional control strategies (Dube, 2024 ; Abinaya et al., 2023 ; Kaul et al., 2018 ). Various nanoparticles, including silver (Ag-NPs), gold (Au-NPs), zinc oxide (ZnO-NPs), and titanium dioxide (TiO₂-NPs), have demonstrated strong antimicrobial activity against a wide range of aquatic pathogens (Mahmud and Haque, 2025 ; Ahmed et al., 2024 ; Aly et al., 2023 ; Cheng et al., 2009 ) (Table 6 ). For instance, ZnO-NPs have been shown to inhibit multiple bacterial and fungal pathogens, such as Aeromonas hydrophila , Edwardsiella tarda , Flavobacterium branchiophilum , Citrobacter spp., Staphylococcus aureus , Vibrio spp., Bacillus cereus , and Pseudomonas aeruginosa (Swain et al., 2014 ). AgNPs are particularly effective due to their ability to release Ag⁺ ions, which bind to membrane proteins, disrupt cellular respiration, and induce bacterial cell death (Lara et al., 2010 ). To enhance biosafety and sustainability, increasing attention has been given to biologically synthesized nanoparticles using medicinal plants, algae, and microbial sources (Mahanty et al., 2013 ). Vaseeharan et al. ( 2010 ) reported reduced mortality in juvenile shrimp ( Fenneropenaeus indicus ) infected with Vibrio harveyi following long-term administration of AgNPs synthesized from Camellia sinensis leaves. Similarly, biogenic AgNPs derived from Caulerpa racemosa effectively prevented Pseudomonas aeruginosa infection in tilapia (Thanigaivel et al., 2022 ). AgNPs biosynthesized by Phormidium formosum also showed strong antimicrobial efficacy against fish pathogens (Elkomy, 2020 ). Furthermore, plant-mediated AgNPs synthesized from Origanum vulgare leaves were reported to be safer and more effective than chemically produced AgNPs, exhibiting dose-dependent inhibition of bacterial pathogens ( Streptococcus agalactiae , Aeromonas hydrophila , Vibrio alginolyticus ) and fungal pathogens ( Aspergillus flavus , Fusarium moniliforme , Candida albicans ) (Ghetas et al., 2022 ). Mani et al. ( 2022 ) further demonstrated that AgNPs synthesized from Persea americana pulp exhibited strong antibacterial activity against Providencia vermicola infections in rohu. In addition, green-synthesized selenium nanoparticles (SeNPs) from Blumea axillaris were shown to effectively combat multidrug-resistant aquatic pathogens, offering an alternative to conventional antibiotics (Dash et al., 2022 ). The multimechanistic mode of action of nanoparticles, including membrane disruption, oxidative stress induction, and interference with cellular metabolism, provides a major advantage over traditional antibiotics, as it may reduce the likelihood of resistance development (Xu et al., 2023 ; Zhu et al., 2024 ). In Bangladesh, the application of nanoparticle-based approaches in aquaculture remains at an early stage and is largely confined to experimental and nutritional interventions (Bashar et al., 2021 ; Ahmed et al., 2026 ) rather than direct medical or therapeutic disease management. Existing studies primarily demonstrate the role of nanoparticles as functional feed additives that enhance growth performance, feed efficiency, and physiological condition, rather than as substitutes for antibiotics in clinical disease treatment. For instance, Bashar et al. ( 2021 ) reported that dietary supplementation of silica nanoparticles at an optimal level (2 mg kg⁻¹ feed) significantly improved growth, feed utilization, and intestinal morphology of Nile tilapia ( Oreochromis niloticus ) without compromising food safety. Similarly, Ahmed et al. ( 2026 ) showed that selenium nanoparticles (SeNPs), particularly at 1.0 mg kg⁻¹ feed, markedly enhanced growth performance, survival, and skeletal development of Asian seabass ( Lates calcarifer ) broodfish reared under recirculatory aquaculture systems, highlighting their value as functional nano-feed additives. Hasan et al. ( 2025 ) further demonstrated that biosynthesized zinc oxide nanoparticles (ZnONPs) improved growth performance, feed efficiency, and survival of striped dwarf catfish ( Mystus vittatus ), with biologically meaningful benefits observed at 110 mg kg⁻¹ feed and no adverse hematological effects. Despite these promising outcomes, nanoparticle applications in Bangladesh have not yet progressed toward therapeutic or farm-level disease control strategies. Adoption is constrained by limited regulatory frameworks, uncertainties regarding environmental fate and food safety, high production costs, and low farmer awareness (Ahmed et al., 2026 ). Nevertheless, given the country’s heavy dependence on antibiotics and the escalating challenge of antimicrobial resistance, green-synthesized and biologically derived nanoparticles hold considerable promise as complementary tools. Future research should prioritize locally sourced nanoformulations, species-specific safety assessments, and field-level validation, alongside standardized toxicity endpoints for cultured fish and non-target aquatic organisms, evaluation of nanoparticle residue accumulation in pond sediments, and potential AMR co-selection risks, to support the responsible integration of nanoparticle-based solutions into sustainable aquaculture health management in Bangladesh. Table 6 Nanoparticles used in aquaculture health management Nanoparticle Host Species Target pathogen Doses Reported effects References Ag NPs Shrimp (L. vannamei) V. harveyi N/A AgNPs reduced bacterial growth to undetectable levels after 4 h of contact, and after 6 h of incubation, almost all treated bacterial cells were dead. Nafisi et al. 2017 Fe 2 O 3 NPs Tilapia ( O. mossambicus ) B. subtilis , S. aureus , E. coli , and P. aeruginosa 0.1 mg/ml Reduced the toxic effect and improved the hematological and immunological parameters. Sheta et al., 2024 Au NPs Shrimp ( L. vannamei ) V. parahaemolyticus 20 µg/g Histopathological damage was reduced, immune parameters were enhanced, and survival increased to 80% in shrimp challenged with V. parahaemolyticus . Tello et al. 2019 Au NPs Tilapia ( O. mossambicus ) A. hydrophila 100 µg/mL Effectively inhibited Aeromonas hydrophila , reduced mortality in infected tilapia, and significantly improved survival and recovery from bacterial infection in O. mossambicus . Vijayakumar et al., 2017 ZnO NPs Tilapia (O. mossambicus) A. hydrophila and V. parahaemolyticus 2, 5, and 10 mg/g Reduced mortality and enhanced disease resistance of A. hydrophila and V. parahaemolyticus . Fish receiving this diet showed the highest post-challenge survival, indicating a strong immunostimulatory effect. Abinaya et al., 2023 ZnO and Se NPs Rohu (L. rohita ) A. hydrophila ZnO (10 mg/kg) and Se (0.3 mg/kg of feed) Relative percentage survival (RPS) was significantly higher in the treated groups, accompanied by marked improvements in growth performance and non-specific immune responses, including respiratory burst, lysozyme, and myeloperoxidase activities, compared with the control group. Swain et al., 2019 Se NPs Penaeus vannamei V. harveyi N/A Had a good antibacterial activity against V. harveyi . Mansouri-Tehrani et al., 2021 MgO NPs M. rosenbergii PL A. hydrophila 100–500 mg kg − 1 General health and non-specific immunity were improved. Srinivasan et al. 2017 Ag NPs Cyprinus carpio F. johnsoniae 34 µg ml-1 Mortality rate decreased significantly. Shaalan et al. 2020 Ag NPs Labeo rohita A. hydrophila 10,15, and 20 µgKg − 1 Treatment resulted in high survivability, enhanced metabolic activity, improved growth performance, increased immune responses, and effective protection against A. hydrophila . Popoola et al. 2023 Chitosan (C) NPs Tilapia ( O. niloticus ) A. hydrophila 0.5,1 and 2g/kg Serum lysozyme, alternative complement, myeloperoxidase activities, and immunoglobulin M levels were significantly elevated, with the highest survival rate observed in fish fed 2 g/kg when challenged with A. hydrophila . Ibrahim et al. 2021 C NPs Ag NPs Tilapia ( O. niloticus ) P. fluorescence 2.0 g CNPs/kg and 1.0 mg AgNPs/kg diet Both CNPs- and AgNPs-treated groups exhibited enhanced non-specific immune parameters and effective defense against P. fluorescens , with significantly reduced post-infection mortality. Aly et al. 2023 Ag NPs Tilapia ( O. niloticus ) A. veronii 100, 250, 500, and 750 µg/L AgNP treatment enhanced fish survival and improved hematological, immunological, and antioxidant responses while optimizing liver and kidney function, with the most favorable effects observed at 750 µg/L. Elgendy et al. 2022 5.1.5 Immunostimulatory Agents Immunostimulatory agents have attracted considerable attention in healthcare and aquaculture and represent one of the widely investigated areas of applied biomedical and veterinary research. These agents enhance the host’s defense capacity by stimulating innate and, in some cases, adaptive immune responses, thereby increasing resistance to infectious diseases. Immunostimulants evaluated in fish health research can be functionally grouped into nutritional additives, microbial-derived products, phytogenic extracts, and synthetic immunomodulators. Of these, nutritional and phytogenic interventions, together with selected microbial derivatives, have gained practical relevance in aquaculture, whereas hormonal agents and several synthetic compounds remain largely restricted to experimental validation (Dawood et al., 2018 ; Wang et al., 2017 ; Mohapatra et al., 2013 ; Meena et al., 2013 ) (Table 7 ). In aquaculture, immunostimulatory agents function primarily as prophylactic interventions rather than therapeutic treatments and are most effective when administered before disease onset. Immunostimulants enhance disease resistance in fish primarily by activating key components of the innate immune system, including stimulation of leukocyte activity, increased phagocytosis and bactericidal responses, activation of the complement pathway, and elevated lysozyme and immunoglobulin levels; however, as they generally do not induce antigen-specific immunological memory, the resulting protection is typically short-term (Selvaraj et al., 2005 ; Akbar et al., 2022; Mokhtar et al., 2023 ). Due to their non-toxicity, having lower residue concerns than antibiotics, and minimal sensitivity to environmental conditions, immunostimulants are particularly suitable for application during the larval and juvenile stages of fish and shellfish. Historically, adjuvants such as Freund’s Complete Adjuvant (FCA) were among the earliest immunostimulatory agents used in animals and were successfully applied alongside fish bacterins to enhance immune responses (Mastan, 2015 ). Over time, a variety of pathogens affecting aquaculture species have been successfully managed through immunostimulant-based approaches, including bacterial pathogens ( Aeromonas salmonicida , A. hydrophila , Vibrio anguillarum , V. vulnificus , Yersinia ruckeri , Streptococcus spp.), viral agents causing infectious hematopoietic necrosis, viral hemorrhagic septicemia, yellow head disease, and parasitic infections such as Ichthyophthirius multifiliis (Barman et al., 2013 ). Among immunostimulants, β-glucans are the most extensively studied and widely applied in aquaculture. These polysaccharides, primarily derived from yeast and fungal cell walls, have demonstrated strong immunomodulatory effects in numerous aquatic species, including red sea bream ( Pagrus major ) (Dawood et al., 2015 b), rainbow trout ( Oncorhynchus mykiss ) (Lauridsen & Buchmann, 2010 ), rohu ( Labeo rohita ) (Misra et al., 2006 ), koi carp ( Cyprinus carpio koi ) (Lin et al., 2011 ), and mirror carp ( C. carpio ) (Kuhlwein et al., 2014 ). β-glucans enhance phagocytic activity, respiratory burst, and disease resistance, making them reliable immunostimulatory feed additives (Dawood & Koshio, 2016 ). Other naturally derived polysaccharides, such as fucoidan, a sulfated polysaccharide found in brown seaweeds, have also demonstrated strong immunomodulatory and disease-resistance properties in farmed aquatic species (Prabu et al., 2016 ; Isnansetyo et al., 2016 ; Immanuel et al., 2012 ). Song et al. ( 2022 ) reported enhanced antibody (IgM) secretion and improved disease resistance against Aeromonas veronii in crucian carp following supplementation with glucans and Astragalus polysaccharides used as vaccine adjuvants. Similarly, alginate-based compounds have shown promising health benefits; for example, dietary sodium alginate supplementation (0.5%) alleviated high-carbohydrate–diet-induced liver damage and intestinal dysbiosis in Monopterus albus , improving metabolic health and gut microbial balance (Zhu et al., 2024 ). In addition to polysaccharide-based immunostimulants, plant-derived phytobiotics play a significant role within the broader category of immunostimulatory agents. Phytobiotics are obtained from various plant parts and contain bioactive compounds such as phenolics, terpenes, organosulfur compounds, alkaloids, phytosterols, saponins, and polysaccharides (Rachwał et al., 2025). These compounds exhibit antimicrobial, antioxidant, anti-inflammatory, and immunostimulatory activities, making them highly valuable for the management of aquaculture health (Sutili et al., 2018 ; Abdel-Latif et al., 2023 ). Table 7 Immunostimulants used in fish species and their reported effects against pathogens Immuno stimulants Species Pathogen Doses Reported effects References Levamisole Rainbow trout (O. mykiss) Yersinia ruckeri 5,10, 25 µg/ml Increase resistance to infection and higher survivability. Ispir, 2009 Bacterial Lipopolysaccharide (LPS) Rainbow trout (O. mykiss) A. hydrophila 3.75, 7.5, and 15 mg/100 g feed LPS exerted a powerful oxidative burst effect and was a potent mediator of phagocytic, lysozyme, bactericidal, and antiprotease activities. Nya and Austin, 2010 β-glucan Common carp (C. carpio) A. hydrophila 100–1000 µg Significant increase in total blood leucocyte counts and an increase in the proportion of neutrophils and monocytes. Selvaraj et al. 2005 Polygonum minus extracts Rainbow trout (O. mykiss) Yersinia ruckeri 5, 10, and 15 mg/kg Blood lysozyme activity and total Ig showed significantly higher levels. The relative immune gene expressions were upregulated relatively in fish fed Adel et al. 2020 Black seed ( Nigella sativa ) Gilthead sea bream (S. aurata) V. harveyi Basal diet with 2% N. sativa Significant rise in erythrogram (RBCs, HB, and PCV %), leucogram (total differential leucocytic count), serum total protein, and globulin. Enhance non-specific immunity and minimize susceptibility and pathogenicity to V. harveyi Aly et al. 2024 Essential oils of clove basil ( Ocimum gratissimum ) Tilapia (O. niloticus) S. agalactiae 0.5, 1.0% and 1.5% Improved intestinal morphology in infected fish. Brum et al. 2018 Turmeric powder ( Curcuma Longa) Common carp ( C. carpio) A. hydrophila 1.0, 2.0, or 5.0 g Enhance innate immunity, and prevent common carp aermoniosis at a level of 2.0 g/kg diet Abdel-Tawwab et al. 2017 Turmeric (C. longa) Rainbow trout (O. mykiss) A. salmonicida 0, 1, 2, and 4% Hematological values, immune responses, antioxidant capacity, and disease resistance were significantly enhanced. Yonar et al. 2019 Velvet bean (Mucuna pruriens) Mossambicus tilapia (O. Mossambicus) A. hydrophila 0, 2, 4, and 6 g /kg Innate immunity and disease resistance against A. hydrophila were positively enhanced. Musthafa et al. 2018 Ashwagandha (Withania somnifera) Tilapia (O. niloticus) A. hydrophila 0, 2.5%, and 5% Antioxidant enzyme activities, including catalase (CAT), glutathione S-transferase (GST), glutathione (GSH), and superoxide dismutase (SOD), were enhanced in liver and muscle, while glutathione peroxidase (GPx) in muscle and serum total antioxidant capacity (TAC) increased significantly. Zahran et al. 2018 Salvadora persica Tilapia (O. niloticus) A. hydrophila 0.0.5,1,2% Antioxidant enzyme activities increased significantly, accompanied by improved hematological and immunological parameters and enhanced survival. El-latif et al. 2021 Thai ginseng Boesenbergia rotunda Tilapia (O. niloticus) S. agalactiae 0, 5,10, 20, 40 g TG kg − 1 Lysozyme and peroxidase activities in tilapia skin mucus were significantly enhanced, along with increased serum lysozyme and peroxidase levels, phagocytic index, and respiratory burst activity, resulting in significantly improved disease resistance. Van Doan et al. 2019 Assam tea Camellia sinensis Tilapia (O. niloticus) S. agalactiae 0, 1, 2, 4, and 8 g kg − 1 Enhanced humoral and mucosal immunity, improved growth performance, and conferred greater resistance against S. agalactiae. Van Doan et al., 2019 Trigonella foenum-graecum (Fenugreek) Common Carp ( C. carpio ) A. hydrophila 0.5,1,5% Treated fish showed significant increases in erythrocytes, leukocytes, hematocrit, and hemoglobin, resulting in enhanced immunity of Cyprinus carpio against A. hydrophila infection. Syeed et al., 2018 Lemon Peel O. niloticus Clarias gariepinus A. hyrophila 1%, 2% Serum lysozyme activity, myeloperoxidase levels, and phagocytic activity increased in both fish species, accompanied by improved enzymatic antioxidant capacity and immune responses. Rahman et al. 2019 Achyranthes aspera Rohu (L. rohita) A. hydrophila 0.5% Growth performance, immune enzyme activities, and the expression of key immune-related genes in rohu were significantly enhanced, while oxidative stress was reduced. Kumar et al. 2019 Curcumin Common carp (Ctenopharyngodon idella) A. hydrophila 0, 196.11, 393.67, 591.46, and 788.52 mg/kg diet Increased lysozyme (LYZ) and acid phosphatase (ACP) activities, elevated complement C3 and C4 levels, and reduced alanine aminotransferase activity, thereby enhancing disease resistance, innate immunity, and antioxidant capacity while attenuating inflammatory responses in fish. Ming et al. 2020 Ginger (Zingiber officinale) Asian sea bass (Lates calcarifer) V. harveyi 1, 2, 3, 5, and 10 g/kg Influenced hematological, biochemical, and immunological parameters, with elevated erythrocyte (RBC) and leukocyte (WBC) counts, thereby strengthening nonspecific immunity and reducing susceptibility to V. harveyi . Talpur et al. 2013 Aloe vera Tilapia (O. niloticus) S. iniae 1% and 2%/kg Increases in red blood cells, hematocrit, hemoglobin, white blood cells, neutrophils, monocytes, eosinophils, serum total protein, and glucose, and no mortality was recorded following the challenge test. Gabriel et al., 2015 Guava leaf extract (Psidium guajava) White shrimp ( P. vannamei) V parahaemolyticus 0, 1, 5, and 10 g kg − 1 Resistance to V. parahaemolyticus was significantly enhanced, with a survival rate of 72.27% and an effective stimulation of the nonspecific immune response. Dewi et al. 2021 Numerous studies have demonstrated that phytobiotics enhance both innate and adaptive immune responses, thereby improving disease resistance and may reduce the need for antibiotics (Awad and Awad, 2017 ; Abdul Kari et al., 2022 ). Beyond immune enhancement, phytobiotics contribute to environmental sustainability by degrading naturally and posing minimal ecological risks compared to synthetic chemicals (Bhanja et al., 2023 ). Organ-level benefits have also been reported, including reduced renal necrosis and inflammation, improved hepatic structure, better lipid metabolism, and enhanced intestinal morphology (Tan et al., 2018 ). For example, dietary supplementation with Psidium guajava leaf extract increased intestinal surface area and nutrient absorption in Oreochromis niloticus , thereby improving growth and health status (Omitoyin et al., 2019 ). Garlic ( Allium sativum ) supplementation has similarly been shown to enhance growth performance, physiological condition, and disease resistance in rohu ( Labeo rohita ) and African catfish ( Clarias gariepinus ) (Sahu et al., 2007 ; Thanikachalam et al., 2010 ). In Bangladesh, the practical application of immunostimulants in aquaculture remains relatively limited and uneven, despite growing experimental evidence supporting their benefits in worldwide. Studies conducted under local farming conditions have demonstrated that plant-derived additives and herbal formulations can enhance growth performance, innate immune responses, and resistance to bacterial pathogens in major cultured species such as carp, tilapia, and pangasius (Faruk et al., 2021 a). However, widespread farm-level adoption is constrained by inadequate standardization of dosage protocols, variability in raw material quality, limited availability of validated commercial products, and insufficient extension support for farmers (Sarker et al., 2023 ). These challenges are further compounded by the dominance of antibiotics as a rapid-response disease management tool in many production systems. Nevertheless, increasing global emphasis on antimicrobial stewardship, residue-free aquaculture products, and environmentally sustainable production practices is expected to accelerate the interest in functional feed additives, including immunostimulants. In this context, Bangladesh presents significant opportunities for the development of locally adapted, low-cost botanical immunostimulant strategies aligned with circular bioeconomy principles and climate-resilient aquaculture frameworks. Strengthening collaborative research, establishing regulatory quality standards, and conducting large-scale participatory field validation will be crucial to bridge the gap between experimental success and commercial adoption. Ultimately, integrating immunostimulant-based health management approaches within broader global efforts to reduce antibiotic dependency can contribute to safer aquatic food systems, improved farmer livelihoods, and enhanced ecosystem sustainability. 5.1.6 Quorum Quenching Bacteria communicate through quorum sensing (QS), a cell-density-dependent signaling system that regulates collective behaviors such as virulence factor production, motility, and biofilm formation. This communication relies on the synthesis, release, and detection of extracellular signaling molecules, enabling bacteria to coordinate pathogenicity and environmental adaptation (Yi et al., 2021 ; Zhong et al., 2021). In aquaculture, several major pathogens, including members of the Vibrionaceae family and the genera Vibrio, Aeromonas, and Pseudomonas, use QS systems to regulate virulence traits that are critical for host colonization and disease progression (Gupta et al., 2022). QS-regulated behaviors, such as flagellated swarming motility, further enhance pathogenicity in some pathogens and promote biofilm formation, increasing resistance to host defenses and conventional antibiotics (Muduli et al., 2021 ; Li et al., 2023 ). Quorum quenching (QQ), which disrupts bacterial communication without killing the pathogen, has emerged as a promising complementary to antibiotics. Unlike conventional antimicrobials, QQ strategies may reduce bactericidal selection pressure and potentially lower resistance selection compared with antibiotics. A wide range of anti-QS compounds including plant-derived molecules such as cinnamaldehyde, eugenol, quercetin, coumaric acid, limonoids, and ajoene have been shown to inhibit QS-regulated pathogenicity across multiple bacterial species (Jakobsen et al., 2012 ; Asfour et al., 2018; Topa et al., 2020 ; Ribeiro et al., 2024 ; Shastri et al., 2025 ). Multiple studies suggest the effectiveness of QQ-producing microorganisms as biocontrol agents in aquaculture (Lubis et al., 2024 ; Khatimah et al., 2024 ). Multiple studies have demonstrated that Bacillus spp. possess intrinsic QQ activity through enzymatic degradation of N-acyl homoserine lactone (AHL) signals. For example, AHL-degrading Bacillus strains significantly suppressed virulence gene expression, swarming motility, and biofilm formation in Vibrio harveyi , resulting in enhanced survival of shrimp post-larvae challenged with luminescent vibriosis (Vinoj et al., 2014 ; Shaheer et al., 2021 ). Similarly, Bacillus licheniformis strains identified by Chen et al. ( 2020 ) disrupted AHL-mediated QS in Aeromonas hydrophila , achieving approximately 70% survival in zebrafish challenge assays, with genomic evidence confirming the presence of AHL-degrading enzymes. Recent studies further reinforce these findings. Bacillus velezensis strains have consistently shown strong QQ activity against Vibrio pathogens. Monzón-Atienza et al. ( 2024 ) reported that B. velezensis D-18 disrupted QS in Vibrio anguillarum via lactonase activity encoded by the ytnP gene, thereby reducing biofilm formation. Likewise, B. velezensis DH82 significantly attenuated Vibrio parahaemolyticus virulence, reduced pathogen abundance in shrimp culture systems, and improved host immune responses in Litopenaeus vannamei (Sun et al., 2022 ). These findings highlight strong agreement on the antivirulence potential of Bacillus -based QQ probiotics. Beyond bacterial probiotics, bioactive compounds from marine and plant sources have also demonstrated QQ efficacy. Saponins extracted from the sea cucumber Holothuria leucospilota significantly inhibited QS-regulated virulence factors in Aeromonas hydrophila by downregulating key QS genes ( ahyI and ahyR ), without exerting bactericidal effects (Payam et al., 2025 ). Similarly, cyanobacteria-derived phenolic compounds produced by Leptolyngbya sp. disrupted QS signaling in Vibrio harveyi by suppressing the LuxP receptor, thereby reducing virulence and pathogen load without inhibiting bacterial growth (Saranya et al., 2025 ). These studies collectively support the concept that QQ-based interventions show potential across diverse biological sources. Despite strong experimental limitations on the efficacy of QQ strategies, their application in aquaculture remains largely confined to laboratory and pilot-scale studies. Disagreements in the literature primarily concern variability in QQ efficacy under complex field conditions, strain specificity, the stability of QQ enzymes in aquatic environments, and challenges associated with large-scale delivery. While in vivo challenge trials consistently demonstrate improved host survival, long-term field validation under commercial farming conditions is still limited. In Bangladesh, quorum quenching has not yet been implemented at the farm level, and no commercial QQ-based products are currently in use. Aquaculture disease management in the country remains heavily reliant on antibiotics, despite increasing evidence of antimicrobial resistance. Nevertheless, the feasibility of QQ strategies in Bangladesh is promising, particularly through the use of locally isolated probiotic Bacillus strains and plant- or algae-derived bioactive compounds. QQ approaches are potentially cost-effective, environmentally benign, and compatible with existing probiotic-based management practices. Future research should prioritize isolating native QQ-producing microbes, evaluating their performance under pond-based farming systems, and integrating them with immunostimulatory and probiotic strategies to develop scalable, antibiotic-free disease control solutions for sustainable aquaculture in Bangladesh. Particular attention should also be given to practical delivery considerations, including the stability of QQ enzymes or signalling-disrupting compounds in effective feed-based incorporation methods, and optimization of dosing frequency under field conditions. 6. Technology Readiness of Antibiotic Alternatives in Bangladeshi Aquaculture To contextualize the experimental evidence presented above, antibiotic alternatives were evaluated using an adapted Technology Readiness Level (TRL) framework reflecting their maturity and adoption status in Bangladeshi aquaculture (Table 8 ). Technology levels were assigned based on predefined criteria, including the scale of validation (laboratory vs pond), reproducibility of biological outcomes, availability of standardized formulations, and regulatory status. The assessment highlights clear disparities between biological efficacy and real-world application. Probiotics, prebiotics, and synbiotics exhibit relatively greater readiness due to extensive experimental validation and partial farm-level adoption, though primarily as growth and health-promoting additives rather than as a disease prevention tool. In contrast, immunostimulants and phytobiotics with promising experimental outcomes but limited and inconsistent field application. Emerging approaches, such as quorum quenching and nanoparticle-based interventions, are confined largely to laboratory and pilot-scale studies, indicating early readiness and no documented large-scale adoption in Bangladesh. Table 8 Adapted technology readiness levels (TRL) and adoption status of antibiotic alternatives in Bangladeshi aquaculture Antibiotic alternative Primary function Global evidence status Adoption status in Bangladesh Adapted TRL* Key limitations for Bangladesh Probiotics Modulation of gut microbiota, immune enhancement, and disease prevention Widely validated through laboratory, field, and commercial applications Commercially available; partially adopted, often without regulation 6–7 Lack of strain standardization, inconsistent product quality, and weak regulatory oversight Prebiotics and Synbiotics Stimulation of beneficial gut microbes and immune response Strong experimental and field evidence globally Limited and fragmented use 5–6 Limited awareness, cost, and formulation challenges Immunostimu- latory agents Enhancement of innate and adaptive immune responses Proven efficacy in controlled trials and some field applications Limited use, mostly experimental 4–5 Cost, inconsistent responses across species, and limited farmer knowledge Vaccines Targeted prevention of specific bacterial and viral diseases Widely used globally in commercial aquaculture Very limited use; species- and disease-specific 3 High cost, cold-chain requirements, limited local availability Nanoparticles Antimicrobial delivery, immune modulation, pathogen control Used globally in commercial farming No reported application in the fields at the farmer's level 2–3 Regulatory uncertainty, safety concerns, and a lack of field validation Quarum Quensing Disruption of bacterial communication and virulence Mostly experimental and proof-of-concept studies No application 1–2 Early-stage research TRL values were adapted to the Bangladeshi aquaculture context based on experimental validation, regulatory readiness, infrastructure availability, and the degree of farm-level adoption, rather than on global technological maturity. 7. Institutional and Regulatory Challenges in Aquaculture Health and Drug Use Universities and higher education institutions play a pivotal role in shaping sustainable aquaculture health management; however, in Bangladesh, this potential appears underutilized. Most fisheries and aquaculture curricula often place limited emphasis on aquatic animal pharmacology, toxicology, antimicrobial stewardship, and rational drug use. Pharmacology-related components are often absent or treated superficially, with minimal practical exposure to disease diagnosis, prescription protocols, withdrawal periods, and mechanisms of antimicrobial resistance. Furthermore, the lack of laboratory-based training in fish disease diagnostics, antimicrobial susceptibility testing, and residue analysis likely constrains graduates' capacity to provide evidence-based health advisory services. Consequently, many aquaculture professionals entering the sector are insufficiently equipped to discourage irrational antibiotic use or to effectively promote alternative disease management strategies. These educational shortcomings are compounded by broader structural deficiencies in diagnostic infrastructure. Most aquaculture-producing regions in Bangladesh lack accessible fish health diagnostic laboratories, and pathogen-specific diagnosis prior to treatment is not routinely practiced. In the absence of diagnostic support, antibiotics are routinely applied as empirical remedies, reinforcing misuse and accelerating the development of antimicrobial resistance. Strengthening linkages among universities, research institutes, and extension services, integrating applied pharmacology and fish health diagnostics into academic curricula, and expanding hands-on training opportunities are, therefore, essential for building a technically competent workforce capable of supporting antibiotic-sparing aquaculture. Economic and production-system constraints further complicate the implementation of alternative health management strategies. The predominance of small-scale and semi-intensive farming systems limits the practicality of injectable vaccines and advanced diagnostic tools, while the relatively high upfront costs of some alternatives, such as vaccines and nano-feed additives, discourage adoption in the absence of targeted subsidies or incentive mechanisms. In addition, limited public–private partnerships and insufficient investment in locally driven innovation restrict the development and scaling of Bangladesh-specific solutions, despite the country’s rich indigenous plant resources and microbial biodiversity that could support low-cost phytobiotics, probiotics, and green-synthesized nanoparticles. Market dynamics further intensify antibiotic dependency. The aquaculture input sector in Bangladesh is characterized by a long and weakly regulated supply chain involving pharmaceutical companies, distributors, dealers, and field-level sales representatives (Ali et al., 2025 ). Antibiotics and chemotherapeutics are actively marketed, often bundled with feed and other inputs, and promoted directly to farmers without veterinary oversight. Company representatives have been reported to influence influence disease management decisions, encouraging antibiotic use even in the absence of confirmed bacterial infections. This practice may disproportionately affects small-scale, low-literacy farmers, who often rely on dealer advice because of limited technical knowledge. As a result, in some farmer communities antibiotics may be perceived as routine growth- and survival-enhancing inputs rather than as last-resort therapeutic agents. Addressing these challenges requires coordinated institutional and policy reform to support the responsible transition toward antibiotic-sparing aquaculture in Bangladesh. Priority actions include strengthening regulatory oversight of aquaculture therapeutics, establishing clear national standards and approval pathways for antibiotic alternatives, and integrating aquaculture more explicitly into national AMR surveillance and broader One Health coordination frameworks. Practical policy instruments, including incentive-based certification schemes for antibiotic-free production, targeted subsidies or credit support for preventive health technologies, and structured capacity-building programs for farmers and extension personnel, could significantly accelerate the adoption of preventive disease management approaches. In parallel, enhanced collaboration among academic and research institutions, regulatory authorities, private feed and pharmaceutical industries, and farmer organizations will be essential to translate laboratory-scale innovations into validated field-level solutions. Without such institutional alignment, regulatory clarity, and sustained investment in knowledge transfer systems, the shift toward sustainable, resilient, and antibiotic-reduced aquaculture production in Bangladesh is likely to remain fragmented and slow, despite strong and growing scientific evidence supporting alternative health management strategies 8. Conclusion This review provides an integrative synthesis of antibiotic use, AMR risks, and the current landscape of antibiotic alternatives in Bangladeshi aquaculture, highlighting both scientific progress and persistent implementation gaps, including insufficient extension support, lack of standardized product evaluation systems, and limited large-scale field adoption. Evidence indicates that the continued reliance on antibiotics, often applied empirically and without proper diagnosis, poses substantial risks to aquatic animal health, environmental integrity, and public health through selection and dissemination of resistant bacteria/genes. Although Bangladesh has made notable advances in aquaculture productivity, health management practices appear not to have evolved at a comparable pace, resulting in a structural dependence on chemotherapeutics. A wide range of antibiotic alternatives, including probiotics, prebiotics, synbiotics, immunostimulants, phytobiotics, vaccines, quorum-quenching strategies, and nanoparticle-based interventions, has strong potential to reduce reliance on antibiotics. Among these, probiotics, prebiotics, and synbiotics exhibit the highest relative readiness, supported by extensive experimental validation and partial farm-level adoption, albeit predominantly as growth- and health-promoting additives rather than antibiotic-sparing disease prevention and control tools. Although immunostimulants, phytobiotics, and vaccines have demonstrated promising biological effectiveness, their broader application remains constrained by insufficient standardization of formulations, dosing protocols, and field validation in Bangladesh. Emerging approaches such as quorum quenching and nanotechnology-based interventions remain at early developmental stages, with evidence largely confined to laboratory and pilot-scale studies and no documented large-scale adoption in Bangladesh. The adapted TRL assessment underscores a substantial disconnect between experimental success and real-world application. This gap is influenced by a lack of scientific evidence, but by institutional, regulatory, economic, and knowledge-based barriers, including inadequate fish health diagnostics, limited pharmacological training, weak regulatory oversight of aquaculture therapeutics, and antibiotic sales from market pressure promotion. The absence of coordinated policy incentives and farmer-centric extension services further hampers the transition toward antibiotic-sparing production systems. Moving forward, a successful reduction in antibiotic dependence will require an integrated strategy that combines science, policy, and practice. Strengthening academic curricula in aquatic pharmacology and disease diagnostics, investing in regional fish health laboratories, regulating antibiotic marketing channels, and reforming national fisheries and AMR-related policies are essential steps. Simultaneously, prioritizing field-level validation, product quality/standardization, cost-effectiveness analysis, and species-specific optimization of antibiotic alternatives will enhance farmer confidence and adoption. With coordinated institutional reform and evidence-based policy support, Bangladesh has a strong opportunity to transition toward sustainable, antibiotic-sparing aquaculture systems that safeguard productivity, environmental health, and food safety. Declarations Data Availability Statement: No datasets were generated or analyzed during the current study. CRediT authorship contribution statement : Conceptualization, M.N.M., M.M.H., and N.A.H; Methodology, M.N.M. and N.A.H; Data curation, M.N.M., M.M.A and N.A.H; Reviewed the literature, M.N.M., S.S., and M.Z.R.J; Writing original draft, M.N.M., M.M.H., and N.A.H; Writing, review & editing, M.N.M., M.M.H., and N.A.H; Supervision, M.M.H and N.A.H. All authors have read and agreed to the published version of the manuscript. Funding: Not applicable Acknowledgments: The authors used Grammarly to improve the readability and language of the manuscript. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article. Ethical approval: Not applicable Conflict of interest: The authors disclosed no conflict of interest to anybody or any organization. References Abd El-Latif, A., Ashraf, M., Abd El-Gawad, E. A., Soror, E. I., Shourbela, R. M., & Zahran, E. (2021). 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Bacterial long-chain polyunsaturated fatty acids: Their biosynthetic genes, functions, and practical use. Marine Drugs, 14 (5), 94. https://doi.org/10.3390/md14050094 Yu, N., Zeng, W., Xiong, Z., & Liu, Z. (2022). A high efficacy DNA vaccine against tilapia lake virus in Nile tilapia ( Oreochromis niloticus ). Aquaculture Reports, 24 , 101166. https://doi.org/10.1016/j.aqrep.2022.101166 Yuan, X., Lv, Z., Zhang, Z., Han, Y., Liu, Z., & Zhang, H. (2023). A review of antibiotics, antibiotic resistant bacteria, and resistance genes in aquaculture: Occurrence, contamination, and transmission. Toxics , 11 (5), 420. https://doi.org/10.3390/toxics11050420 Zahran, E., Abd El-Gawad, E. A., & Risha, E. (2018). Dietary Withania somnifera root confers protective and immunotherapeutic effects against Aeromonas hydrophila infection in Nile tilapia ( Oreochromis niloticus ). Fish & Shellfish Immunology, 80 , 641–650. https://doi.org/10.1016/j.fsi.2018.06.009 Zhong, S., & He, S. (2021). Quorum sensing inhibition or quenching in Acinetobacter baumannii : The novel therapeutic strategies for new drug development. Frontiers in Microbiology, 12 , 558003. https://doi.org/10.3389/fmicb.2021.558003 Zhou, Q. C., Buentello, J. A., & Gatlin, D. M., III. (2010). Effects of dietary prebiotics on growth performance, immune response and intestinal morphology of red drum ( Sciaenops ocellatus ). Aquaculture, 309 (1–4), 253–257. https://doi.org/10.1016/j.aquaculture.2010.09.003 Zhu, W., Zhang, H., Pan, H., Zeng, H., Wang, W., Liu, Y., et al. (2024). Sodium alginate ameliorates health in freshwater fish through gut–liver axis modulation under high carbohydrate diets. Aquaculture Reports, 40 , 102538. https://doi.org/10.1016/j.aqrep.2024.102538 Zhu, X., Tang, Q., Zhou, X., & Momeni, M. R. (2024). Antibiotic resistance and nanotechnology: A narrative review. Microbial Pathogenesis, 193 , 106741. https://doi.org/10.1016/j.micpath.2024.106741 Zokaeifar, H., Balcázar, J. L., Saad, C. R., Kamarudin, M. S., Sijam, K., Arshad, A., & Nejat, N. (2012). Effects of Bacillus subtilis on the growth performance, digestive enzymes, immune gene expression and disease resistance of white shrimp, Litopenaeus vannamei . Fish & Shellfish Immunology, 33 (4), 683–689. https://doi.org/10.1016/j.fsi.2012.05.027 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9386222","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":621846906,"identity":"576ebabf-2b2f-4311-9e77-ca55eaaef95a","order_by":0,"name":"Md. Naim Mahmud","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIie3QMUvEMBTA8VcCcXmla4onfoVI4Y6icl8l4UBntw4dDsS4HM4Kh5+h080pgboUbi3Y5Tjo5FAXR7m0m0N7NzrkvyXkl0cC4HL9y7wlQJJiQIjO20T3ewxAd/sjpCwm4bOSe1aeRDqlyA1flRH31QlkdmaeMqAUORNTFr7Xl1yT/BOhvhgi8UqqCnCCMybu2MOmuco0XVwjNNEQ4bojjGL8KgoWboyXaZyeIxg5SLY7SzhBXknF/LWZZzr4GSdVN0VYUhrC/aWRdgo9QuwUoQu0n+ztWdEs3gyN4jUfecv2vqm+f9N5QII2b9P69uXjcVd9JcM/1if+rEh/1dh5l8vlch3rAIMRZMKYOgzmAAAAAElFTkSuQmCC","orcid":"","institution":"Bangladesh Agricultural University","correspondingAuthor":true,"prefix":"","firstName":"Md.","middleName":"Naim","lastName":"Mahmud","suffix":""},{"id":621846911,"identity":"791c293e-7846-417d-9565-283b73d35389","order_by":1,"name":"Md. Zihad Rahman Jony","email":"","orcid":"","institution":"Bangladesh Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Md.","middleName":"Zihad Rahman","lastName":"Jony","suffix":""},{"id":621846913,"identity":"1f7cfe96-89f8-4657-a435-9aa8b0baeed7","order_by":2,"name":"Sanchari Sakidar","email":"","orcid":"","institution":"Bangladesh Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Sanchari","middleName":"","lastName":"Sakidar","suffix":""},{"id":621846917,"identity":"9e4d729a-6dc3-4c81-ab8e-d8ac8ef67e54","order_by":3,"name":"Neaz A. Hasan","email":"","orcid":"","institution":"Gopalganj Science and Technology University","correspondingAuthor":false,"prefix":"","firstName":"Neaz","middleName":"A.","lastName":"Hasan","suffix":""},{"id":621846918,"identity":"8daf6a1a-35f1-4478-aa6e-d543f83ad33e","order_by":4,"name":"Md. Mehedi Alam","email":"","orcid":"","institution":"Khulna Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Md.","middleName":"Mehedi","lastName":"Alam","suffix":""},{"id":621846925,"identity":"63c8ed56-72df-4f0f-ab65-cc3757bd3829","order_by":5,"name":"Mohammad Mahfujul Haque","email":"","orcid":"","institution":"Bangladesh Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Mahfujul","lastName":"Haque","suffix":""}],"badges":[],"createdAt":"2026-04-11 08:53:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9386222/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9386222/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106895355,"identity":"11118908-792f-4255-b574-8cec341bee05","added_by":"auto","created_at":"2026-04-14 14:12:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":220805,"visible":true,"origin":"","legend":"\u003cp\u003eMajor mechanisms of bacterial antibiotic resistance in aquaculture (Created by Biorender).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9386222/v1/050c736190b13bc34b533b6e.png"},{"id":106895353,"identity":"fb4357c5-f02a-45ce-b5d0-e6a0cf68688a","added_by":"auto","created_at":"2026-04-14 14:12:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":162258,"visible":true,"origin":"","legend":"\u003cp\u003eNon-antibiotic approaches for disease management in aquaculture species (Created by Biorender)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9386222/v1/345e498c02b59c44370350e1.png"},{"id":108806487,"identity":"9f807ec0-4fc4-464e-be92-4fea6ba7eb3e","added_by":"auto","created_at":"2026-05-08 15:28:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1868660,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9386222/v1/e2185045-d732-4c53-9ac5-4d2f99530944.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Breaking Antibiotic Dependency in Aquaculture: Evaluating Alternative Disease Management Strategies for Sustainable Aquaculture in Bangladesh","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAntibiotics are widely recognized as effective therapeutic agents for the treatment of infectious diseases (Afroze et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). The broader term \u0026ldquo;\u003cem\u003eantimicrobials\u003c/em\u003e\u0026rdquo; encompasses antibacterial, antifungal, antiparasitic, and antiviral agents (Leekha et al., \u003cspan citationid=\"CR127\" class=\"CitationRef\"\u003e2011\u003c/span\u003e), among which antibiotics play a central role by inhibiting bacterial growth or eliminating pathogenic bacteria. These compounds are therefore essential in both human and veterinary medicine for the management of infectious diseases (Done et al., \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). However, the extensive and often indiscriminate use of antibiotics has accelerated the emergence of antimicrobial resistance (AMR), now recognized as one of the most severe global public health threats.\u003c/p\u003e \u003cp\u003eA global systematic analysis estimated that 1.27\u0026nbsp;million deaths were directly attributable to bacterial antimicrobial resistance, while 4.95\u0026nbsp;million deaths were associated with resistant infections worldwide in 2019, with projections suggesting that this figure could rise to approximately 10\u0026nbsp;million deaths per year by 2050 if effective mitigation strategies are not implemented (Murray et al., \u003cspan citationid=\"CR160\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Salam et al., \u003cspan citationid=\"CR189\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Ahmed et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Beyond health impacts, AMR poses substantial economic risks. According to World Bank projections, under a high-impact AMR scenario, global gross domestic product (GDP) could decline by 3.8% by 2050, with an estimated annual economic loss of USD 3.4 trillion by 2030 (World Bank, 2017). Antibiotic resistance also undermines the safety and feasibility of critical medical interventions, including surgical procedures, cancer chemotherapy, and organ transplantation, all of which rely heavily on effective antimicrobial prophylaxis (Ahmed et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Ho et al., \u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe rapid spread of antibiotic resistance is largely attributed to the overuse and misuse of antibiotics across multiple sectors, including human healthcare, agriculture, animal husbandry, and food production systems (Ahmed et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Globalization further exacerbates this challenge by facilitating the transboundary dissemination of resistant bacteria and resistance genes, thereby posing risks even to regions with relatively prudent antibiotic use practices (Laxminarayan et al., \u003cspan citationid=\"CR124\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Stein et al., 2014; Barlam and Gupta, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Alarmingly, several pathogenic bacteria of major human health concern, including \u003cem\u003eEscherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii\u003c/em\u003e, and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, have already developed resistance to multiple, and in some cases many, classes of antibiotics, posing a serious challenge to effective clinical treatment (Murray et al., \u003cspan citationid=\"CR160\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; WHO, 2017; Afroze et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAgainst this backdrop, aquaculture has been identified as an emerging pathway for the development and dissemination of antimicrobial resistance (AMR), especially in low- and middle-income countries where regulatory frameworks, antibiotic stewardship, and surveillance systems are often fragmented or insufficiently implemented (FAO, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Cabello et al., \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). The rapid expansion of aquaculture has been driven by increasing global demand for animal protein, declining wild fish stocks due to overfishing and pollution, and the need to ensure food security for a growing human population (Alfiko et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Fantatto et al., \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Mahmud et al., \u003cspan citationid=\"CR140\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Since 1990, global aquaculture production has increased by more than 650%, reaching a record 130.9\u0026nbsp;million metric tons (MT) in 2022, of which 94.4\u0026nbsp;million MT comprised aquatic animals (FAO, 2024; Ritchie, \u003cspan citationid=\"CR185\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Asia accounts for over 91% of global aquaculture production (FAO, 2024). However, intensified farming practices aimed at maximizing productivity often increase susceptibility to bacterial, viral, fungal, and parasitic diseases, thereby promoting reliance on chemotherapeutic agents, including antibiotics (Salma et al., \u003cspan citationid=\"CR191\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile antibiotics have historically supported productivity in aquaculture, practices such as prophylactic use, nonprescription access, incorrect dosing, and inadequate compliance with withdrawal periods have raised significant ecological and public health concerns (Chowdhury et al., \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Kawsar et al. \u003cspan citationid=\"CR108\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Antibiotic residues can accumulate in aquatic environments and in fish tissues, and continuous exposure can create selective pressure that favors the emergence and persistence of resistant microbial populations (Bhat et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Furthermore, the horizontal transfer of antibiotic resistance genes among aquatic bacteria may increases the likelihood of resistance transmission to human pathogens, amplifying risks across the food\u0026ndash;environment\u0026ndash;health nexus (Jeon et al., \u003cspan citationid=\"CR106\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBangladesh represents a particularly important case study within this global context. As one of the world\u0026rsquo;s leading fish-producing nations, Bangladesh recorded total fish production of 5.018\u0026nbsp;million MT in 2023\u0026ndash;2024, with aquaculture accounting for 59.34% of national output (DoF, 2023). Over the past three decades, aquaculture has become one of the fastest-growing agro-food sectors in the country. Inland aquaculture production more than doubled from 1.006\u0026nbsp;million MT in 2007\u0026ndash;08 to 2.852\u0026nbsp;million MT in 2022\u0026ndash;23 (DoF, 2023; Haque and Mahmud, \u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). This rapid expansion has been reported to be influenced by widespread use of veterinary drugs and aqua-medicines, often driven by farmers\u0026rsquo; preferences, disease pressure, and market availability rather than evidence-based guidelines.\u003c/p\u003e \u003cp\u003eConsequently, antibiotic-resistant bacteria have been widely reported in aquaculture environments, cultured fish, and surrounding water bodies in Bangladesh, raising concerns for food safety, ecosystem health, and consumer protection (Salma et al. \u003cspan citationid=\"CR190\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Ahmed et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Chowdhury et al. \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Khan et al., \u003cspan citationid=\"CR109\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Ripon et al., \u003cspan citationid=\"CR184\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Nayem et al., \u003cspan citationid=\"CR165\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). The detection of antibiotic residues in export-oriented aquaculture products further threatens international market access and compliance with stringent food safety regulations, potentially undermining the economic sustainability of the sector.\u003c/p\u003e \u003cp\u003eIn response to these challenges, alternative disease management strategies have gained increasing attention as sustainable approaches to reduce antibiotic dependency and mitigate AMR risks in aquaculture. These strategies include the use of probiotics, prebiotics, phytobiotics, immunostimulants, vaccines, bacteriophages, and improved biosecurity and farm management practices (Bondad-Reantaso et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Elgendy et al., \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Rahayu et al., \u003cspan citationid=\"CR179\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; AlQurashi et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Rasul et al., \u003cspan citationid=\"CR182\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Such interventions aim to enhance host immunity, stabilize microbial communities, and prevent disease outbreaks with reduced risk of selecting for antibiotic resistance compared with antibiotics that drive antimicrobial resistance. Nevertheless, their effectiveness and adoption remain highly variable, influenced by species-specific responses, culture systems, environmental conditions, regulatory frameworks, and socio-economic constraints (Mahmud et al., \u003cspan citationid=\"CR140\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Despite the growing body of global literature on antibiotic alternatives in aquaculture, evidence specific to Bangladesh remains fragmented and insufficiently synthesized. There are a few comprehensive reviews that critically evaluate the efficacy, feasibility, and limitations of non-antibiotic disease management strategies within Bangladeshi aquaculture systems, while simultaneously considering farmer-level adoption barriers, regulatory challenges, and economic implications.\u003c/p\u003e \u003cp\u003eTherefore, this review aims to systematically synthesize existing knowledge on alternatives to antibiotics in the aquaculture sector of Bangladesh. Specifically, it evaluates the effectiveness of non-antibiotic disease control strategies, assesses their potential to reduce AMR risks, and identifies key research gaps and practical constraints hindering large-scale implementation. By integrating scientific evidence with policy and management perspectives, this review seeks to support the development of sustainable, antibiotic- sparing aquaculture systems in Bangladesh.\u003c/p\u003e"},{"header":"2. Methodology","content":"\u003cp\u003eThis review was conducted following the methodological guidance of the Joanna Briggs Institute (JBI) for evidence synthesis in scoping reviews (Peters et al., \u003cspan citationid=\"CR172\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The JBI framework was adopted to ensure methodological transparency and systematic identification of relevant literature. The review aimed to synthesize existing evidence on alternative disease management strategies to reduce antibiotic dependency in aquaculture systems of Bangladesh, guided by predefined inclusion and exclusion criteria and a structured search strategy (Mahmud and Haque, \u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Literature Search Strategy\u003c/h2\u003e \u003cp\u003eA comprehensive literature search was conducted to identify relevant peer-reviewed and grey literature on alternative disease management strategies in aquaculture. Electronic database searches were performed in PubMed, Scopus, Web of Science, and ScienceDirect, while Google Scholar was additionally used to capture relevant studies not indexed in major databases. The search strategy integrated controlled vocabulary (e.g., MeSH terms in PubMed) and free-text keywords combined using Boolean operators, with database-specific syntax applied to improve search sensitivity and precision. The final search was completed on 15 February 2025. In Scopus, the search string TITLE-ABS-KEY (aquaculture OR \u0026ldquo;fish farming\u0026rdquo; OR \u0026ldquo;shrimp culture\u0026rdquo;) AND TITLE-ABS-KEY (\u0026ldquo;antibiotic alternatives\u0026rdquo; OR probiotics OR prebiotics OR phytobiotics OR vaccines OR immunostimulants OR biosecurity OR \u0026ldquo;disease management\u0026rdquo;) AND TITLE-ABS-KEY (Bangladesh OR \u0026ldquo;tropical aquaculture\u0026rdquo; OR \u0026ldquo;developing countries\u0026rdquo;) was used to ensure reproducible retrieval of relevant studies. Grey literature was identified through targeted searches of reports and policy documents from international and national organizations, including the Food and Agriculture Organization (FAO), World Health Organization (WHO), and the Department of Fisheries (DoF), Bangladesh, as well as relevant NGO publications.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Inclusion and Exclusion Criteria\u003c/h2\u003e \u003cp\u003eTo ensure the relevance, quality, and applicability of the selected literature, studies were screened using predefined eligibility criteria (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe study\u0026rsquo;s eligibility and exclusion criteria (followed by Gambelli et al. \u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e2019\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCriterion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDescription\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInclusion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eExclusion\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTimeframe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAfter 2000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore 2000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of Language\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnglish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-English\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of Literature\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeer-reviewed literature, government, and organizational reports\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNews articles and non-scientific web content lacking analytical or empirical basis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea of Content\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudies addressing non-antibiotic disease management strategies in aquaculture, including probiotics, prebiotics, phytobiotics, immunostimulants, vaccines, nanoparticles, biosecurity measures, and integrated health management approaches\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-aquaculture sectors (e.g., terrestrial agriculture, livestock, poultry)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePublication Status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePublished and available online\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePublished but not accessible\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeographic Coverage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAquaculture-producing countries were included to derive comparative insights and identify disease management strategies applicable to Bangladeshi aquaculture.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome Reporting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDisease resistance, survival, growth performance, environmental sustainability, economic feasibility, or farm-level applicability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudies lacking clear outcome indicators\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethodologies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudies employing experimental, observational, and field-based methods.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudies with unclear design, insufficient methodological detail, or unsupported claims.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data Extraction\u003c/h2\u003e \u003cp\u003eData were extracted from the selected studies using bibliographic details (authors, year of publication, journal), study location, culture system, and target species. Methodological characteristics were recorded, including the study design (experimental, observational, field trial, or review), the type of disease management strategy evaluated, and the duration of interventions. Outcome variables extracted encompassed indicators of fish health and performance (e.g., disease incidence, survival rate, immune response, growth performance), environmental impacts, economic feasibility, and practical constraints related to implementation. Quantitative and qualitative findings were synthesized using narrative and thematic approaches to evaluate the effectiveness and applicability of alternative disease management strategies across studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Categorization and Synthesis of Evidence\u003c/h2\u003e \u003cp\u003eThe extracted data were categorized based on the type of alternative disease management strategy, including probiotics and prebiotics, phytobiotics, immunostimulants, vaccines, nanoparticles, and improved biosecurity and farm management practices. Evidence synthesis involved a comparative evaluation of the effectiveness and limitations of each approach within the context of Bangladeshi aquaculture. The effectiveness was assessed based on the reported direction and magnitude of outcomes, including changes in disease incidence, survival rate, growth performance, and immune response indicators. Emphasis was placed on identifying patterns, consistencies, and discrepancies across studies, while highlighting system-specific and species-specific responses.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Critical Analysis and Interpretation\u003c/h2\u003e \u003cp\u003eA critical appraisal of the synthesized literature was conducted to evaluate the scientific robustness, practical relevance, and contextual applicability of alternative disease management strategies in aquaculture. The analysis emphasized nutritional and immunological benefits, host sensitivity to pathogen exposure, environmental sustainability, and scalability at the farm level. Particular attention was given to how these alternatives align with existing farmer practices, regulatory frameworks, and resource constraints in Bangladesh.\u003c/p\u003e \u003cp\u003eTo contextualize the maturity and real-world applicability of antibiotic alternative interventions, an adapted Technology Readiness Level (TRL) framework was applied. Interventions were classified along a qualitative scale from early conceptual or laboratory validation (TRL 1\u0026ndash;3), controlled pilot or experimental farm testing (TRL 4\u0026ndash;5), field-scale demonstration and partial farmer adoption (TRL 6\u0026ndash;7), to commercially established and widely implemented practices (TRL 8\u0026ndash;9) (Mankins, \u003cspan citationid=\"CR143\" class=\"CitationRef\"\u003e1995\u003c/span\u003e; Yfanti, and Sakkas, \u003cspan citationid=\"CR241\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Balafoutis et al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The TRL assignment was based on reported evidence regarding validation scale, regulatory or commercial availability, and documented adoption in aquaculture systems. To ensure consistency, predefined decision criteria were applied, and interventions were comparatively assessed across studies describing similar implementation contexts. Based on this integrated assessment, key research gaps, institutional bottlenecks, and implementation challenges were identified. These insights were used to highlight priority areas for future research, policy refinement, and capacity development, supporting a structured transition toward sustainable, antibiotic-sparing aquaculture health management in Bangladesh.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Antibiotic Use in Aquaculture of Bangladesh","content":"\u003cp\u003eIntensive aquaculture practices in Bangladesh are characterized by high stocking densities, sub-optimal hygienic conditions, and multiple physical and environmental stressors, including overcrowding, frequent handling and transportation, predation pressure, inappropriate lighting and noise exposure, and fluctuating water quality parameters such as pH, temperature, dissolved oxygen, nitrite, and turbidity (Chowdhury et al., \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). These stressors weaken fish's immune responses and increase their susceptibility to infectious diseases. The presence of emerging pathogens and their intensification has led to a widespread dependence on antimicrobials, particularly antibiotics, for disease prevention and control. Antibiotics are commonly applied as therapeutic and prophylactic agents to reduce disease-induced mortality and prevent bacterial infections in Bangladesh. These compounds are often administered directly into pond water or applied as top-coated formulations on commercial fish feeds (Mahmud et al., \u003cspan citationid=\"CR140\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Okocha et al., \u003cspan citationid=\"CR168\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). However, the improper and unregulated use of antibiotics has raised significant concerns about antimicrobial resistance, environmental contamination, and food safety. Numerous studies have reported the presence of antibiotic residues in aquaculture environments and farmed fish products. The most commonly detected antibiotics in aquaculture water are tetracyclines, macrolides, fluoroquinolones, and sulfonamides (Afroze et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Residues of trimethoprim, sulfamethoxazole, norfloxacin, and oxytetracycline acid have been detected in shrimp ponds, sediments, and adjacent canals (Haque et al., \u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Barman et al., \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Hasan et al. (\u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) reported oxytetracycline (OTC) residues in live fish and transport water samples collected from markets in Mymensingh district, Bangladesh. OTC was detected in 13 fish and 5 water samples during summer and in 8 fish samples during winter, with overall residue positivity of 5.42% in fish and 8.33% in water. Concentrations in fish ranged from 10.80 to 77.55 ppb, with the highest prevalence observed in pangas (16.67%). Chowdhury et al. (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) reported that 71% of fish farms in Mymensingh, Cumilla, Bagerhat, Jashore, Khulna, and Satkhira used antibiotics during the production cycle, with oxytetracycline, ciprofloxacin, and amoxicillin being the most commonly used, often applied without prescription.\u003c/p\u003e \u003cp\u003eRegion-specific investigations further highlight the scale and diversity of antibiotic use across the country. Kawsar et al. (\u003cspan citationid=\"CR108\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) documented the use of 30 different antibiotics under multiple trade names in fish farms in the Narsingdi region, with oxytetracycline (26%), erythromycin (19%), and sulfamethoxazole (17%) being the most commonly applied active ingredients, followed by ciprofloxacin (14%), enrofloxacin (9%), chlortetracycline (6%), and amoxicillin (5%). In shrimp farms of the south-western coastal region, commonly used antibiotics included oxytetracycline, chlortetracycline, amoxicillin, co-trimoxazole, sulphadiazine, and sulphamethoxazole (Shamsuzzaman and Biswas, \u003cspan citationid=\"CR200\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). In contrast, studies from south-eastern districts such as Cumilla, Chandpur, and Feni identified erythromycin, oxytetracycline, chlortetracycline HCl, and doxycycline as the most frequently used antibiotics in aquaculture operations (Hossain et al., \u003cspan citationid=\"CR92\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntibiotics used in the Aquaculture of Bangladesh in different regions (Adopted from Bari et al. 2024; Rasul et al. \u003cspan citationid=\"CR182\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Salma et al. \u003cspan citationid=\"CR191\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Kawsar et al. \u003cspan citationid=\"CR108\" class=\"CitationRef\"\u003e2022\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrand Name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eActive Ingredients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDose\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProducers\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCipro-Avet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.05 mL/1\u0026ndash;2 kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACME Laboratories Ltd\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCiproflox\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCiprofloxacin hydrochloride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e250 mg/1\u0026ndash;2 kg of feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSK\u0026thinsp;+\u0026thinsp;F Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevoflox\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.61 mg/L of water for 3\u0026ndash;5days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDrug International Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicronid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eErythromycin, sulfadiazine, trimethoprim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5000 mg/kg feed for 3\u0026ndash;5 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRenata Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeomin-50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeomycin sulphate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e500 mg/1\u0026ndash;1.5 L of water\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLocal supplier\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxy-D vet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline-20%\u003c/p\u003e \u003cp\u003eDoxycyline-10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5000\u0026ndash;10,000 mg/kg body weight of fish for 5\u0026ndash;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEon Animal Health Products Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxysenthin 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline HC1 BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e500\u0026ndash;1000 mg/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNovartis Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRanamox\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmoxicillin trihydrate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e300\u0026ndash;400 mg/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRenata Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenaflox\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCiprofloxacin hydrochloride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e500 mg/1\u0026ndash;1.5 L water\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRenata Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenamycin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e300\u0026ndash;420 mg/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRenata Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenatrim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSulfadiazine, trimethoprim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026ndash;5 mL/kg feed for 3\u0026ndash;5 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRenata Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOtetra-vet 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSquare Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiomycin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBiopharma Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAquamycine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACI Animal Health Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEST-Vet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eErythromycin thiocyanate, sulphadiazine, trimethoprim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026ndash;5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEon Animal Health Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCotrim-vet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSulphamethoxazole, trimethoprim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSquare Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSulprim-vet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSulphadyazine, trimethoprim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026ndash;5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSquare Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAT-vet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSulphadyazine, trimethoprim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026ndash;5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACME Laboratories Ltd\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eErisen-vet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eErythromycin, sulphadiazine, trimethoprim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSquare Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCiprocin-Vet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSquare Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTurbonid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eErythromycin, sulphadiazine, trimethoprim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEskayef Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenaquine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFlumequine 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026ndash;5 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRenata Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevomax\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLevofloxacin 10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEskayef Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaxtor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChlortetracycline 45%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEskayef Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEska'CTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChlortetracycline 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEskayef Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnroflox DS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnrofloxacin BP 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026ndash;5 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEskayef Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAugment vet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmoxicillin trihydrate BP \u0026amp; clavulanate BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEskayef Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBactitap\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline hydrochloride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACI Animal Health Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEryvet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eErythromycin sulphadiazine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACI Animal Health Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFRA C12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1-Monolaurin \u0026amp; essential oil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACI Animal Health Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCiprovet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCiprofloxacin 10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEon Animal Health Product Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEon CTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChlortetracycline 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEon Animal Health Product Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCF-vet-20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 gm/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePrapti Animal Health\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNovoflor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFlorfenicol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u0026ndash;2 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEskayef Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCidaflox\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOpsonin Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFlumequine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFlumequine BP 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 ml/kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEon Animal Health Product Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAquamysine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChlortetracycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1-1.5 kg/ton feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFishtech BD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmoxifish\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmoxicillin trihydrate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u0026ndash;5 g/ kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFishtech BD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBactitab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 g/kg body weight for 5\u0026ndash;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACI Animal Health Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcimox (vet) Powder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmoxicillin trihydrate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 g/1 kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACI Animal Health Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxysentin 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline HCl BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100\u0026ndash;200 g/100 kg feed for 5\u0026ndash;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNovartis Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChlorsteclin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChlorotetracycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200\u0026ndash;300 g/100 kg feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNovartis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrgamycins 15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline HCl BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 g/100 kg for 10 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOrganic Pharma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrgacycline 15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChlortetracycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200\u0026ndash;300 g/100 kg feed (5\u0026ndash;7 days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOrganic Pharma\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxin WS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 g/kg body weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNavana Pharma Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOtetravetpowder\u003c/p\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOxytetracycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u0026ndash;16 g/100 kg\u003c/p\u003e \u003cp\u003ebody weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSquare Pharmaceuticals Ltd\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSulphatrim\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSulphadiazine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50g/kg body\u003c/p\u003e \u003cp\u003eweight,5\u0026ndash;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSquare Pharmaceuticals Ltd.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEnvironmental monitoring studies indicate widespread antibiotic contamination in aquaculture-associated surface waters in Bangladesh. Salma et al. (\u003cspan citationid=\"CR190\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) detected 26 antibiotics from seven classes, with sulfadiazine, sulfamethoxazole, trimethoprim, erythromycin-H₂O, and amoxicillin occurring most frequently; sulfadiazine reached concentrations up to 25,000 ng L⁻\u0026sup1;, particularly in striped catfish (\u003cem\u003ePangasianodon hypophthalmus\u003c/em\u003e) ponds. Several compounds posed a high ecological risk and exerted strong selective pressure on antimicrobial resistance. Consistently, Faruk et al. (\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) reported intensive antibiotic use in aquaculture farms of the Mymensingh region, where Oxytetracycline and amoxicillin were the most commonly used, followed by ciprofloxacin and sulfadiazine, supplied mainly by major national pharmaceutical companies. Across regions, antibiotic selection and dosing in aquaculture are largely guided by farmers\u0026rsquo; personal experience, package instructions, and advice from chemical vendors, reflecting limited knowledge of antibiotic modes of action and the absence of prescription-based regulation. Salma et al. (\u003cspan citationid=\"CR191\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) reported that in the Rajshahi district of Bangladesh, 88% of fish farmers lacked expertise regarding aqua-chemical and antibiotic use, while 81% were unaware of appropriate dosages. Limited access to diagnostic infrastructure further promotes the empirical use of antibiotics, particularly among small-scale farmers (Chowdhury et al., \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Such non-judicious use accelerates the emergence and spread of antimicrobial resistance and disrupts aquatic microbial communities, posing risks to animal, public, and ecosystem health and sustainability (Chowdhury et al., \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e"},{"header":"4. AMR in Aquaculture Systems of Bangladesh","content":"\u003cp\u003eAntimicrobial-resistant bacteria are widely detected across the interconnected domains of the environment, animals, and humans, underscoring the importance of a One Health perspective for understanding the emergence and dissemination of resistance (Robinson et al., \u003cspan citationid=\"CR186\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Bacteria can pump antibiotics out of the cell, modify drug target sites, or enzymatically degrade antibiotics. They may also alter cell wall permeability to prevent drug entry. Additionally, resistance genes can spread through horizontal gene transfer, enhancing bacterial survival (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A comprehensive understanding of AMR evolution and transmission dynamics across this triad is essential for anticipating emerging pathogens and designing effective mitigation strategies. Prolonged and often unregulated antibiotic use in aquaculture systems can accelerate the development of resistance in both farmed fish and associated bacterial communities and may contribute to its dissemination into surrounding ecosystems (Cabello et al., \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Woźniacka et al., \u003cspan citationid=\"CR236\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Important bacterial genera associated with aquaculture environments include \u003cem\u003eAeromonas\u003c/em\u003e (e.g., \u003cem\u003eA. hydrophila\u003c/em\u003e), \u003cem\u003eVibrio\u003c/em\u003e (e.g., \u003cem\u003eV. parahaemolyticus\u003c/em\u003e), \u003cem\u003eStaphylococcus\u003c/em\u003e (e.g., \u003cem\u003eS. aureus\u003c/em\u003e), \u003cem\u003ePseudomonas\u003c/em\u003e (e.g., \u003cem\u003eP. aeruginosa\u003c/em\u003e), \u003cem\u003eSalmonella\u003c/em\u003e spp., and \u003cem\u003eEscherichia coli\u003c/em\u003e, some of which are recognized as opportunistic or zoonotic pathogens of public health concern (Boss et al., \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; He et al., 2016; Budiati et al., \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Kitiyodom et al., \u003cspan citationid=\"CR115\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). In Bangladesh, inadequate regulation and widespread use of antibiotics in aquaculture pose significant risks to aquatic animal health, environmental integrity, and public health (Salma et al., \u003cspan citationid=\"CR191\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral studies have documented extensive antimicrobial resistance among bacterial isolates recovered from cultured fish in Bangladesh. Hossain et al. (\u003cspan citationid=\"CR94\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) identified 58 bacterial isolates belonging to nine genera from fish samples, with \u003cem\u003eKlebsiella\u003c/em\u003e spp., \u003cem\u003ePseudomonas\u003c/em\u003e spp., \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003eVibrio\u003c/em\u003e spp., and \u003cem\u003eE. coli\u003c/em\u003e being most prevalent. Alarmingly, all isolates exhibited complete resistance (100%) to tetracyclines, penicillins, cephalosporins, aminoglycosides, and macrolides, while resistance rates of approximately 80% were reported for sulfonamides and fluoroquinolones. Pathogen-specific investigations further highlight the severity of AMR in Bangladeshi aquaculture. Siddique et al. (\u003cspan citationid=\"CR205\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) reported a high prevalence of \u003cem\u003eVibrio parahaemolyticus\u003c/em\u003e in aquaculture farms of Satkhira, coastal Bangladesh, isolated from water, sediment, tilapia, rui, and shrimp. The occurrence of this pathogen was positively correlated with elevated temperature and salinity. Several isolates harbored the virulence gene \u003cem\u003etrh\u003c/em\u003e, indicating potential pathogenicity. These isolates were further confirmed using molecular (PCR) and phenotypic identification methods, with exceptionally high resistance (94.1%) to ampicillin and amoxicillin. Genetic analyses revealed diverse yet related resistant strains, indicating a substantial public health and aquaculture disease risk in the region. Similarly, Foysal et al. (\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e2011\u003c/span\u003e) isolated \u003cem\u003ePseudomonas fluorescens\u003c/em\u003e from carp and catfish exhibiting hemorrhagic septicemia, indicating its possible role as an associated or opportunistic pathogen, and evaluated its antibiotic susceptibility profile. While isolates remained sensitive to streptomycin and gentamicin, resistance to chloramphenicol was widespread, and approximately 80% of isolates exhibited multidrug resistance (MDR). Khan et al. (\u003cspan citationid=\"CR109\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) assessed bacterial isolates from shrimp farms in Bagerhat district and reported that 78.0% were resistant to at least one antibiotic, and 29.3% were MDR to commonly used antibiotics, including ampicillin, oxytetracycline, ciprofloxacin, and azithromycin. Studies focusing on shrimp culture systems further confirm the persistence of resistant \u003cem\u003eVibrio\u003c/em\u003e species. Hossain et al. (\u003cspan citationid=\"CR96\" class=\"CitationRef\"\u003e2012\u003c/span\u003e) detected \u003cem\u003eVibrio\u003c/em\u003e spp. in shrimp pond water and harvested black tiger shrimp (\u003cem\u003ePenaeus monodon\u003c/em\u003e), with higher contamination levels observed in market samples compared to farm-level samples. Antibiotic susceptibility testing revealed the highest resistance to penicillin and cephalexin (28.57%), and MDR was detected in at least one isolate. The authors suggested these patterns to indiscriminate antibiotic use during culture and post-harvest contamination during handling and marketing. In the Khulna region, Haque et al. (\u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) reported \u003cem\u003eVibrio\u003c/em\u003e spp. in 34% of shrimp farming\u0026ndash;associated samples, with significantly higher prevalence in shrimp (54%) than in mud (26%) or water (22%). Dominant species included \u003cem\u003eVibrio cholerae\u003c/em\u003e, \u003cem\u003eV. parahaemolyticus\u003c/em\u003e, and \u003cem\u003eV. alginolyticus\u003c/em\u003e, with resistance rates ranging from 15.7% to 92.2% against ampicillin, amikacin, cefotaxime, tetracycline, ceftazidime, gentamicin, nalidixic acid, levofoxacin, and ciprofoxacin. Notably, more than half (52.9%) of the isolates were multidrug-resistant, highlighting a critical food safety concern. Recent evidence suggests that AMR is also highly prevalent in freshwater aquaculture systems. Sultana et al. (\u003cspan citationid=\"CR213\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) reported an exceptionally high occurrence of \u003cem\u003eV. cholerae\u003c/em\u003e and \u003cem\u003eV. parahaemolyticus\u003c/em\u003e in tilapia and rui cultured in Bangladesh, as well as in fish scales, gut samples, and tank water. \u003cem\u003eV. cholerae\u003c/em\u003e was detected in 100% of tilapia and 92.3% of rui samples, while \u003cem\u003eV. parahaemolyticus\u003c/em\u003e was present in over 92% of both species. Antibiotic susceptibility assays showed moderate resistance to aztreonam and ciprofloxacin, but high sensitivity to gentamicin and ceftriaxone. Multidrug resistance was observed in 12% of \u003cem\u003eV. cholerae\u003c/em\u003e and 37.5% of \u003cem\u003eV. parahaemolyticus\u003c/em\u003e isolates, and a small proportion of \u003cem\u003eV. parahaemolyticus\u003c/em\u003e exhibited extreme drug resistance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBeyond bacterial isolates, the presence of antibiotic residues in fish tissues and aquatic environments further is consistent with ongoing exposure and selective pressure. Nayem et al. (\u003cspan citationid=\"CR165\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) detected residues of ciprofloxacin, oxytetracycline, chlortetracycline, levofloxacin, and enrofloxacin in commercially farmed fish species, including tilapia, stinging catfish, climbing perch, and pabda, using TLC and UHPLC techniques. Although hazard quotient values were below unity, suggesting no immediate toxic risk, the persistence of residues raises concerns regarding chronic exposure and AMR development. Consistent with these findings, antibiotics such as sulfamethoxazole, trimethoprim, tylosin, sulfadiazine, and amoxicillin have been detected at ng L⁻\u0026sup1; concentrations in surface waters of freshwater finfish and brackish-water shellfish farms, with higher detection frequencies in finfish systems (Hossain et al., \u003cspan citationid=\"CR93\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). While preliminary ecological and resistance risk assessments indicated risk quotients below one, the widespread occurrence of antibiotics in farm waters highlights continuous environmental exposure and reinforces the need for improved antibiotic stewardship, surveillance, and wastewater management in aquaculture. Taken together, the widespread occurrence of antimicrobial-resistant pathogens and antibiotic residues in Bangladeshi aquaculture underscores the limitations of antibiotic-dependent disease management. These findings highlight the urgent need to transition to effective non-antibiotic alternatives that can reduce disease burden without exacerbating selection pressures for resistance. Sustainable approaches such as probiotics, prebiotics, immunostimulants, phytobiotics, vaccines, and emerging technologies therefore represent promising options for future aquaculture health management strategies. Evaluating the feasibility and applicability of these alternatives is essential for ensuring long-term productivity, environmental safety, and public health protection.\u003c/p\u003e"},{"header":"5. Alternative Therapies for Controlling Fish Diseases in Aquaculture","content":"\u003cp\u003eNumerous alternative disease management strategies have been developed worldwide to overcome the limitations associated with conventional antibiotic use in aquaculture, including the emergence of AMR, accumulation of drug residues in aquatic products and environments, and increasing regulatory restrictions on antibiotic application. These approaches aim to control infectious diseases while minimizing the selection for antibiotic resistance and reducing residue-related risks. Key alternatives include probiotics, prebiotics, synbiotics, immunostimulants, vaccination, quorum-quenching agents, antimicrobial peptides, biosurfactants, bacteriocins, and nanotechnology-based interventions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Many of these strategies function by enhancing host immunity, modulating gut microbiota, disrupting pathogen virulence mechanisms, or preventing pathogen colonization rather than directly killing microorganisms. While several alternatives, such as probiotics, limited commercial use of nanoparticles, and vaccines in some species, including \u003cem\u003eOreochromis niloticus, Cyprinus carpio\u003c/em\u003e, \u003cem\u003eOncorhynchus mykiss\u003c/em\u003e, and \u003cem\u003eLates calcarifer\u003c/em\u003e, are already applied in commercial aquaculture systems worldwide, others, including quorum-quenching compounds, bacteriophages, and antimicrobial peptides are still being evaluated for effective large-scale application (Rahman et al. \u003cspan citationid=\"CR181\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Kim et al. \u003cspan citationid=\"CR114\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Ibrahim et al. \u003cspan citationid=\"CR99\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Aly et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Musthafa et al. \u003cspan citationid=\"CR162\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe effectiveness and adoption of these alternatives vary depending on species, culture systems, environmental conditions, and management practices. In parallel, the development of accurate and rapid disease diagnostic technologies is increasingly recognized as a critical component of sustainable aquaculture health management, as it enables timely pathogen identification, supports the targeted application of alternatives such as vaccines, probiotics, and antimicrobial peptides, and reduces the reliance on empirical antibiotic treatments. Early and precise pathogen detection enables timely intervention, reduces unnecessary antibiotic use, and supports the application of targeted, non-antibiotic therapies.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003cdiv class=\"Heading\"\u003e5.1.1 Vaccines\u003c/div\u003e \u003cp\u003eVaccination is widely recognized as one of the most effective approaches for preventing a broad spectrum of bacterial and viral diseases in aquaculture and contributes substantially to the environmental, social, and economic sustainability of fish farming systems. An ideal fish vaccine is expected to elicit a specific and long-lasting immune response while providing robust protection against target pathogens (Mu\u0026ntilde;oz-Atienza, 2021). Globally, fish are vaccinated annually, and in several aquaculture-intensive regions, disease management strategies have progressively shifted from antibiotic dependence toward vaccination-based control (Ma et al., \u003cspan citationid=\"CR136\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). The introduction of vaccines has led to a dramatic reduction in antibiotic use in fish farming, establishing vaccination as a cost-effective and sustainable method for controlling infectious diseases in aquaculture. Advances in molecular biology and improved understanding of protective antigens have accelerated the development of next-generation vaccines for both animal and human health applications (Brun et al., \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2011\u003c/span\u003e; Kim et al., \u003cspan citationid=\"CR113\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Frietze et al., \u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Consequently, countries such as China, Japan, and Norway have successfully integrated vaccination programs into their aquaculture practices, highlighting global recognition of vaccines as essential tools for effective health management (Gudding and Van Muiswinkel, \u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Currently, a wide range of vaccine types are available for aquaculture, including DNA vaccines, recombinant vaccines, and conventionally produced formulations, many of which have been approved for use in specific fish species (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Based on preparation methods, aquaculture vaccines are commonly classified as live attenuated, inactivated (killed), subunit, and vectored vaccines. Conventional vaccines, particularly live attenuated and inactivated formulations, remain widely used due to their proven ability to induce strong and specific immune responses in fish. At the same time, molecular and recombinant vaccine technologies offer more targeted, safer, and adaptable approaches, representing promising advances in sustainable disease-prevention strategies for modern aquaculture systems (Mondal and Thomas, \u003cspan citationid=\"CR154\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVaccination strategies targeting key pathogens in aquaculture species\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccine type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTarget pathogen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHost species\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDelivery method\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEfficacy (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReferences\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLive Attenuated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eEdwardsiella ictaluri\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChannel catfish (\u003cem\u003eIctalurus punctatus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbdelhamed et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2018\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyvalent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStreptococcosis, Lactococcosis, and Enterococcosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTilapia (\u003cem\u003eOreochromis niloticus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI/P and Immersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbu-Elala et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBivalent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eListonella anguillarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eJuvenile sea bass (\u003cem\u003eDicentrarchus labrax\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92\u0026ndash;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAngelidis et al. \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2006\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDNA vaccine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKoi herpesvirus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCommon carp\u003c/p\u003e \u003cp\u003e\u003cem\u003eCyprinus carpio\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAonullah et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2017\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBivalent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eVibrio vulnificus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFreshwater eel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOral, I/P and Immersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEsteve-Gassent et al., \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e2004\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLGA encapsulated inactivated (killed)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eViral haemorrhagic septicaemia virus (VHSV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOlive flounder (\u003cem\u003eParalichthys olivaceus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmersion and oral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60\u0026ndash;73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKole et al. \u003cspan citationid=\"CR117\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInactivated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVHSV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOlive flounder\u003c/p\u003e \u003cp\u003e\u003cem\u003e(P. olivaceus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72\u0026ndash;89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHwang et al. \u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e2017\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInactivated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eV. anguillarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTurbot (\u003cem\u003eScophthalmus maximus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59\u0026ndash;81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eWang et al. \u003cspan citationid=\"CR234\" class=\"CitationRef\"\u003e2016\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInactivated recombinant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eFrancisella noatunensis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNile tilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. niloticus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI/P\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eShahin et al. \u003cspan citationid=\"CR199\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormalin-killed vaccine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eStreptococcus\u003c/em\u003e, \u003cem\u003eEnterococcus\u003c/em\u003e, and \u003cem\u003eLactococcus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNile tilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. niloticus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI/P) and bath immersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60\u0026ndash;88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAkter et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2022\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBivalent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eAeromonas\u003c/em\u003e sp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCatfishes (\u003cem\u003eHeteropneustes fossilis\u003c/em\u003e, \u003cem\u003eClarias batrachus\u003c/em\u003e, and \u003cem\u003ePangasius pangasius\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIM and oral routes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e88\u0026ndash;93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRahman et al. \u003cspan citationid=\"CR181\" class=\"CitationRef\"\u003e2022\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecombinant subunit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhite spot syndrome virus (WSSV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eShrimp\u003c/p\u003e \u003cp\u003e(\u003cem\u003eL. vannamei\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOral administration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKim et al., \u003cspan citationid=\"CR114\" class=\"CitationRef\"\u003e2023\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecombinant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWSSV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eShrimp\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOral administration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLanh et al., \u003cspan citationid=\"CR121\" class=\"CitationRef\"\u003e2021\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInactivated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eV. anguillarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRainbow trout (\u003cem\u003eO. mykiss\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI/P\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLim et al. \u003cspan citationid=\"CR129\" class=\"CitationRef\"\u003e2023\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLive vaccine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eV. anguillarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTiger puffer (\u003cem\u003eTakifugu rubripes)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80\u0026ndash;90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLiu et al. \u003cspan citationid=\"CR132\" class=\"CitationRef\"\u003e2018\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInactivated whole-cell bivalents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eV. alginolyticus\u003c/em\u003e and \u003cem\u003eS. agalactiae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI/P\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70\u0026ndash;90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbotaleb et\u0026nbsp;al. 2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInactivated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eF. columnare\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRed tilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eOreochromis\u003c/em\u003e sp.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImmersion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKitiyodom et\u0026nbsp;al. 2019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInactivated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eV. vulnificus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTurbot (\u003cem\u003eScophthalmus maximus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI/M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53\u0026ndash;63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGu et\u0026nbsp;al. 2021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eI. multifiliis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eChannel catfish (\u003cem\u003eIctalurus punctatus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eI/P\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eXu et\u0026nbsp;al. 2020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia lake virus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNile tilapia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYu et\u0026nbsp;al. 2022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn Bangladesh, vaccination against streptococcosis has been experimentally evaluated but remains limited evidence of routine farm-level adoption. Akter et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) demonstrated that a whole-cell formalin-killed \u003cem\u003eEnterococcus\u003c/em\u003e vaccine administered to Nile tilapia via intraperitoneal injection and bath immersion significantly enhanced immune responses (RBC, WBC, and IgM levels) and reduced mortality following challenge, with relative percent survival reaching up to 88.6% and 69.1%, respectively. Rahman et al. (\u003cspan citationid=\"CR181\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) also reported that a bivalent inactivated vaccine prepared from \u003cem\u003eAeromonas hydrophila\u003c/em\u003e and \u003cem\u003eA. veronii\u003c/em\u003e, administered via intramuscular and oral routes to brood fish, significantly enhanced hematological parameters and IgM antibody levels in brood fish, larvae, and eggs. Vaccinated groups showed markedly higher relative percent survival (RPS) in larvae of shing, magur, and pangas (exceeding 88\u0026ndash;93%) following pathogen challenge compared to non-vaccinated controls. Despite demonstrating strong protective efficacy and transgenerational immune benefits under controlled conditions, such vaccination strategies remain largely confined to experimental settings and have not been effectively scaled up for routine farm-level implementation in Bangladesh. Despite the proven effectiveness of vaccination in aquaculture, its adoption in Bangladesh remains limited due to several structural and operational constraints. These include the absence of locally produced, species-specific vaccines, limited cold-chain infrastructure, and high costs associated with vaccine procurement and delivery. Moreover, the lack of licensed commercial fish vaccines and the limited availability of commercial suppliers in the domestic market have further constrained large-scale implementation. Additionally, the predominance of small-scale and extensive farming systems complicates mass vaccination, particularly for injectable vaccines. Inadequate diagnostic capacity and limited awareness among farmers regarding vaccine benefits further restrict uptake. Lack of coordinated national vaccination programs also hinders widespread implementation. Addressing these barriers through targeted research, capacity building, and policy support is essential for integrating vaccination into sustainable aquaculture health management in Bangladesh.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003cdiv class=\"Heading\"\u003e5.1.2 Probiotics\u003c/div\u003e \u003cp\u003eProbiotics are defined as live microorganisms which, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO, 2002). They are widely used worldwide as dietary supplements in food and feed formulations and commonly include bacterial genera such as Bacillus spp., \u003cem\u003eLactobacillus\u003c/em\u003e, and \u003cem\u003eBifidobacterium\u003c/em\u003e, as well as certain yeast strains (Bondad-Reantaso et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). In aquaculture, probiotics play an important role in enhancing nutrition, improving feed utilization, strengthening immune responses, and increasing resistance to infectious diseases (Rahayu et al., \u003cspan citationid=\"CR179\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Unlike antibiotics, which act primarily through bactericidal or bacteriostatic mechanisms but can also disrupt host-associated microbiota and ecological balance, probiotics exert their beneficial effects through multiple biological pathways, including competitive exclusion of pathogens, modulation of host immune responses, enhancement of digestive processes, and stabilization of microbial communities. These include competitive exclusion of pathogenic microorganisms, inhibition of pathogen adhesion and colonization, production of antimicrobial compounds such as bacteriocins, enhancement of intestinal barrier integrity, reduction of intestinal pH, and modulation of host immune responses (Williams et al., 2010). Extensive research has demonstrated that probiotic supplementation can significantly improve growth performance, feed conversion efficiency, immune competence, and overall health status of cultured aquatic species, while also contributing to improved water quality in farming systems (Tabassum et al., \u003cspan citationid=\"CR219\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Although antibiotics have historically played a key role in controlling bacterial diseases in aquaculture, their widespread and often unregulated use has contributed to antimicrobial resistance, residue accumulation, and ecological imbalances within cultured systems (Mahmud \u0026amp; Haque, \u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). In response, probiotics are increasingly promoted as safer and more sustainable disease-management alternatives. Experimental evidence suggests the effectiveness of probiotics in disease prevention. Taoka et al. (\u003cspan citationid=\"CR222\" class=\"CitationRef\"\u003e2006\u003c/span\u003e) demonstrated that feeding viable probiotics to \u003cem\u003eOreochromis niloticus\u003c/em\u003e significantly enhanced non-specific immune responses, including lysozyme activity, neutrophil migration, and bactericidal activity, thereby increasing resistance against \u003cem\u003eEdwardsiella tarda\u003c/em\u003e. Probiotics have also been shown to synthesize essential nutrients, such as polyunsaturated fatty acids and vitamin B₁₂, contributing to host nutrition regardless of their localization within the gut, water column, or sediment (Eichmiller et al., \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Yoshida et al., \u003cspan citationid=\"CR244\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Recent studies further highlight species- and strain-specific probiotic effects. Shija et al. (\u003cspan citationid=\"CR204\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) reported that dietary supplementation with \u003cem\u003eBacillus amyloliquefaciens\u003c/em\u003e AV5 for 30 days significantly increased lysozyme levels in both serum and skin mucus of Nile tilapia compared to control groups. Similarly, Nikoskelainen et al. (\u003cspan citationid=\"CR166\" class=\"CitationRef\"\u003e2001\u003c/span\u003e) observed reduced mortality in fish fed diets containing \u003cem\u003eLactobacillus rhamnosus\u003c/em\u003e following challenge with virulent \u003cem\u003eAeromonas salmonicida\u003c/em\u003e. Optimal probiotic inclusion levels, typically ranging from 10⁴ to 10⁸ CFU g⁻\u0026sup1; of feed, have been shown to stimulate respiratory burst activity, thereby enhancing disease resistance (Nayak, \u003cspan citationid=\"CR164\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). In addition, \u003cem\u003ePhaeobacter inhibens\u003c/em\u003e, known for producing the antimicrobial compound tropodithietic acid (TDA), has demonstrated strong inhibitory effects against the larval pathogen \u003cem\u003eVibrio anguillarum\u003c/em\u003e in copepods, highlighting its potential application as a probiotic in live feed systems. Al-Dohail et al. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2011\u003c/span\u003e) further demonstrated that dietary supplementation with \u003cem\u003eLactobacillus acidophilus\u003c/em\u003e significantly improved haematological and biochemical parameters, liver and kidney health, and resistance to \u003cem\u003eStaphylococcus xylosus\u003c/em\u003e, \u003cem\u003eAeromonas hydrophila\u003c/em\u003e, and \u003cem\u003eStreptococcus agalactiae\u003c/em\u003e in African catfish (\u003cem\u003eClarias gariepinus\u003c/em\u003e). Collectively, these findings indicate that probiotics are effective biocontrol agents and sustainable tools for disease management in modern aquaculture.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOverview of probiotics used in disease management in aquaculture\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbiotic Strain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHost species\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePathogen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReported effects\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReferences\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLacticaseibacillus rhamnosus\u003c/em\u003e FS3051, \u003cem\u003eLimosilactobacillus reuteri\u003c/em\u003e FS3052, and \u003cem\u003eBacillus subtilis natto\u003c/em\u003e NTU-18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrey mullet (\u003cem\u003eMugil cephalus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eNocardia seriolae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eImmune gene expression was enhanced, while reducing Mycoplasma and Rhodobacter, which were negatively correlated with immune responses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eChan et al. \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2024\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCarnobacterium maltaromaticum\u003c/em\u003e B26 and \u003cem\u003eCarnobacterium divergens\u003c/em\u003e B33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRainbow trout (\u003cem\u003eOncorhynchus mykiss\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. salmonicida\u003c/em\u003e and \u003cem\u003eYersinia ruckeri.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEnhanced both cellular and humoral immune responses, increased respiratory burst activity, and elevated lysozyme levels in serum and gut mucosa.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKim and Austin, \u003cspan citationid=\"CR112\" class=\"CitationRef\"\u003e2006\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKocuria\u003c/em\u003e SM1 and \u003cem\u003eRhodococcus\u003c/em\u003e SM2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRainbow trout\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. mykiss\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. anguillarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEnhanced innate immune responses through increased activity of cell wall proteins and whole cell proteins, leading to elevated bacterial killing activity, leukocyte counts, and immunoglobulin levels.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSharifuzzaman et al. \u003cspan citationid=\"CR201\" class=\"CitationRef\"\u003e2011\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRoseobacter\u003c/em\u003e 27\u0026thinsp;\u0026minus;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTurbot (\u003cem\u003eScophthalmus maximus\u003c/em\u003e) larvae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. anguillarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProtected against \u003cem\u003eV. anguillarum\u003c/em\u003e infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePlanas et al., \u003cspan citationid=\"CR173\" class=\"CitationRef\"\u003e2006\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLactobacillus sakei\u003c/em\u003e BK19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eOplegnathus fasciatus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eE. tarda\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncrease innate immunity levels and Serum complement and antiprotease activities. Altered hematological parameters.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHarikrishnan et al., \u003cspan citationid=\"CR88\" class=\"CitationRef\"\u003e2011\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLactobacillus pentosus\u003c/em\u003e PL11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJapanese eel \u003cem\u003eAnguilla japonica\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eE. tarda\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePlasma immunoglobulin M levels, CAT and SOD activities, Hematological parameters, and mieloperoxidase were significantly higher, improving health performance.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLee et al. \u003cspan citationid=\"CR125\" class=\"CitationRef\"\u003e2013\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLactococcus lactis\u003c/em\u003e BFE920\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOlive flounder (\u003cem\u003eParalichthys olivaceus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eStreptococcus iniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInnate immunity activated by the \u003cem\u003eL. lactis\u003c/em\u003e administration: increased lysosomal activity, disease resistance against pathogens.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKim et al. 2013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elactic acid bacterium \u003cem\u003ePediococcus pentosaceus\u003c/em\u003e strain 4012 (LAB4012)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroupers (\u003cem\u003eEpinephelus\u003c/em\u003e spp.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. anguillarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLeukocyte abundance in peripheral blood and the phagocytic activity of head-kidney phagocytes were altered, indicating modulation of the immune response.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHuang et al., \u003cspan citationid=\"CR97\" class=\"CitationRef\"\u003e2014\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus casseliflavus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRainbow trout \u003cem\u003eOncorhynchus mykiss\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. iniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 Weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSignificantly improved gut health, innate immunity, and disease resistance, as reflected by increased serum protein, albumin, IgM, leukocyte counts, and neutrophil levels.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSafari et al.2016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEnterococcus gallinarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSea bass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. anguilarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProduced a moderated protective effect against \u003cem\u003eV. anguillarum\u003c/em\u003e infection.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSorroza et al., \u003cspan citationid=\"CR209\" class=\"CitationRef\"\u003e2013\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLc. lactis\u003c/em\u003e BFE920 and \u003cem\u003eLb. plantarum\u003c/em\u003e FGL0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOlive flounder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. iniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEnhanced skin mucus lysozyme activity and the phagocytic activity of innate immune cells, indicating a clear immunostimulatory effect.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBeck et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2015\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSaccharomyces cerevisiae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNile tilapia,\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. niloticus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThe lowest fish mortality and bacterial counts were obtained.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbdel-Tawwab et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2008\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eStreptomyces\u003c/em\u003e strains CLS-28, CLS-39, CLS-45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ePenaeus monodon\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eVibrio harveyi\u003c/em\u003e and \u003cem\u003eV. proteolyticus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHigher survival compared\u0026nbsp;to the control against the pathogen.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDas et al. \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2010\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eB. subtilis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShrimp (\u003cem\u003eLitopenaeus vannamei\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eVibrio harveyi\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAll immune-related genes were significantly up-regulated, resulting in disease resistance through an enhanced immune response in shrimp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eZokaeifar et al. \u003cspan citationid=\"CR252\" class=\"CitationRef\"\u003e2012\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBacillus subtilis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHybrid grouper (Epinephelus fuscoguttatus\u0026times; E. lanceolatus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. harveyi\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDecreased the expression of both inflammation and apoptosis-related genes, modulating immunity.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHan et al. \u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e2024\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLactobacillus plantarum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eLitopenaeus vannamei\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. alginolyticus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotal hemocyte count increased, indicating improved immunity and disease resistance, without adverse effects on growth performance or hepatopancreas morphology.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLee et al. \u003cspan citationid=\"CR126\" class=\"CitationRef\"\u003e2024\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eB. subtilis\u003c/em\u003e\u003c/p\u003e \u003cp\u003eand \u003cem\u003eLactobacillus\u003c/em\u003e spp.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eLabeo rohita\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. veronii\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProbiotic-treated fish exhibited significantly enhanced gut immunological parameters, improved hepatic cellular organization with more regular nuclei and reduced intercellular spaces, and the highest post-challenge survival rate.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFerdous et al. \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e2024\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactobacillus plantarum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eOncorhynchus mykiss\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncreases in RBC, hemoglobin (Hb), MCH, MCHC, and MCV were observed, accompanied by enhanced resistance against \u003cem\u003eA. hydrophila\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSoltani et al. \u003cspan citationid=\"CR206\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactobacillus casei\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eCyprinus carpio\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIntestinal enzyme activities, including ALP, lipase, amylase, trypsin, and protease, were significantly elevated.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMohammadian et al. \u003cspan citationid=\"CR151\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eB. subtilis\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eL. plantarum\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eP. aeruginosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eLabeo rohita\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSerum lysozyme activity, as well as phagocytic and respiratory burst activities in head kidney macrophages of \u003cem\u003eL. rohita\u003c/em\u003e, increased significantly.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGiri et al. \u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e2014\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn Bangladesh, probiotics are used in aquaculture; however, their application is primarily oriented toward growth promotion and feed efficiency rather than as deliberate alternatives to antibiotics or other antimicrobial agents. Commercial probiotic products are widely available and are commonly used to improve water quality, enhance digestion, and accelerate growth performance in cultured fish and shrimp. Despite growing awareness of antimicrobial resistance, probiotics are limited evidence of using in a targeted manner for disease prevention or pathogen control at the farm level. Several laboratory- and hatchery-based studies conducted in Bangladesh have demonstrated the efficacy of probiotics against important bacterial pathogens, including \u003cem\u003eAeromonas\u003c/em\u003e, \u003cem\u003eVibrio\u003c/em\u003e, and \u003cem\u003eStreptococcus\u003c/em\u003e species. These studies reported enhanced immune responses, reduced mortality, and improved resistance under controlled experimental conditions (Ferdous et al. \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Hossain et al. \u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). However, large-scale field validation and systematic farm-level application remain limited. Constraints such as inconsistent product quality, lack of strain-specific recommendations, limited farmer knowledge, and absence of regulatory guidelines hinder the wider adoption of probiotics as true antimicrobial alternatives (Hossain et al., 2023). Consequently, although probiotics are increasingly used for growth promotion and water quality improvement, their specific application as a disease-prevention strategy to reduce antibiotic dependency in Bangladeshi aquaculture remains underutilized.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003cdiv class=\"Heading\"\u003e5.1.3 Prebiotics and Synbiotics\u003c/div\u003e \u003cp\u003ePrebiotics are defined as non-digestible substrates that beneficially influence the host by selectively stimulating the growth and activity of health-promoting microorganisms in the gastrointestinal tract (Lordan et al., \u003cspan citationid=\"CR134\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Srirengaraj et al., \u003cspan citationid=\"CR211\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Commonly used prebiotic compounds in aquaculture include mannan oligosaccharides (MOS), fructooligosaccharides (FOS), arabinooligosaccharides (AOS), β-glucans, inulin, chitosan and other functional polysaccharides, which are recognized for their roles in enhancing innate immunity, gut health, and disease resistance in aquatic organisms (Geraylou et al., \u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Khanjani et al., \u003cspan citationid=\"CR110\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Among these, MOS is one of the commonly used prebiotics in animal and fish diets, owing to its capacity to improve growth performance, feed utilization, survival rates, immune responses, and antagonistic activity against aquatic pathogens (Mustafa et al., \u003cspan citationid=\"CR161\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Xue et al., \u003cspan citationid=\"CR239\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Several studies have demonstrated that prebiotics exert their beneficial effects primarily by modulating gut microbiota composition, stimulating immune function, and enhancing resistance to infectious diseases in both finfish and shellfish. For instance, an effective prebiotic is characterized by resistance to host digestive enzymes, lack of absorption in the foregut, fermentability by gut microbiota, and selective stimulation of beneficial bacterial populations, ultimately leading to improved host health and physiological condition (Goh et al., \u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Experimental evidence further supports the stress-mitigating and immunoprotective roles of prebiotics. Xue et al. (\u003cspan citationid=\"CR239\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) demonstrated that dietary MOS significantly enhanced growth performance, digestive enzyme activity, antioxidant capacity, and innate immune responses in common carp under ammonia stress, while also reducing liver, gill, and intestinal tissue damage. Similarly, Mustafa et al. (\u003cspan citationid=\"CR161\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) reported that dietary FOS significantly altered the gut microbial community structure of Pacific white shrimp (\u003cem\u003eLitopenaeus vannamei\u003c/em\u003e), highlighting the capacity of prebiotics to modulate intestinal microbiota, although growth and immune responses were not significantly affected during short-term feeding trials.\u003c/p\u003e \u003cp\u003eSynbiotics, defined as synergistic combinations of probiotics and prebiotics, have gained increasing attention due to their combined capacity to enhance gut microbial balance and host immunity more effectively than either component alone (Hardi et al., \u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Ye et al. (\u003cspan citationid=\"CR240\" class=\"CitationRef\"\u003e2011\u003c/span\u003e) demonstrated that synbiotic diets containing FOS, MOS, and \u003cem\u003eBacillus clausii\u003c/em\u003e significantly improved growth performance, digestive enzyme activity, lysozyme-mediated immunity, and lipid metabolism in Japanese flounder, resulting in superior health outcomes compared with single probiotic or prebiotic treatments. Likewise, Pawar et al. (\u003cspan citationid=\"CR170\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) showed that synbiotic supplementation in feed (0.5% FOS\u0026thinsp;+\u0026thinsp;10⁶ CFU g⁻\u0026sup1; \u003cem\u003eBacillus subtilis\u003c/em\u003e) markedly enhanced immune responses and post-challenge survival of \u003cem\u003eLabeo fimbriatus\u003c/em\u003e fingerlings against \u003cem\u003eAeromonas hydrophila\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eIn Bangladesh, recent studies suggest the potential relevance of prebiotics and synbiotics as sustainable alternatives to antibiotics in aquaculture. Munni et al. (\u003cspan citationid=\"CR158\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) demonstrated that dietary supplementation with prebiotics and synbiotics significantly improved growth performance, feed efficiency, and immune indicators in Nile tilapia compared with antibiotic-treated groups, with synbiotics yielding the highest body weight and white blood cell counts without inducing pathological liver alterations. Similarly, Linda et al. (\u003cspan citationid=\"CR131\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) reported that synbiotic supplementation enhanced intestinal health, hematological parameters, and liver histology in Asian stinging catfish (\u003cem\u003eHeteropneustes fossilis\u003c/em\u003e), conferring greater host resilience and reduced disease susceptibility.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOverview of Prebiotics and Synbiotics used in aquaculture health management\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrebiotics/mixtures \u0026amp; Synbiotics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHost species\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMode of application\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDuration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReported effects\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReferences\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFOS, GOS, MOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRed drum \u003cem\u003e(Sciaenops ocellatus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 g/kg diet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIntestinal enzyme activities, including ALP, lipase, amylase, trypsin, and protease, were significantly elevated.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eZhou et al. \u003cspan citationid=\"CR249\" class=\"CitationRef\"\u003e2010\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInulin, GOS, soybean oligosaccharide (SBO)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex reversed red hybrid tilapia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5% of diet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFish fed the diet containing 5% GOS exhibited the lowest post-challenge mortality rate.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePlongbunjong et al. \u003cspan citationid=\"CR174\" class=\"CitationRef\"\u003e2011\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-glucan, MOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCommon carp (\u003cem\u003eC. carpio\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u0026ndash;2.5 g/kg diet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eImprove the feed efficiency and growth performance of\u0026nbsp;\u003cem\u003eC.\u0026nbsp;carpio\u003c/em\u003e\u0026nbsp;fingerlings as well as their resistance to\u0026nbsp;\u003cem\u003eA.\u0026nbsp;hydrophila\u003c/em\u003e\u0026nbsp;infection.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEbrahim et al. 2012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-glucan, GOS, MOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSnakehead\u003c/p\u003e \u003cp\u003e(\u003cem\u003eChanna striata\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eβ-glucan (2 g/kg diet), GOS (5 g/kg diet), MOS (5 g/kg diet)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThe treatment proved optimal for growth performance and enhanced the expression of immune regulatory genes in \u003cem\u003eChanna striata\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMunir et al. \u003cspan citationid=\"CR157\" class=\"CitationRef\"\u003e2016\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-glucan, MOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCaspian trout (\u003cem\u003eSalmo trutta\u003c/em\u003e caspius)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMOS (4 g/kg diet) +β-glucan (4 g/kg diet)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHumoral innate immunity was enhanced, accompanied by reduced transcription of inflammation-related genes.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eJami et al. \u003cspan citationid=\"CR105\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-glucan, MOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShabout\u003c/p\u003e \u003cp\u003e(\u003cem\u003eTor grypus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5, 1, and 1.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAt a 1.5% inclusion level, the diet positively influenced growth performance, carcass protein content, intestinal microflora, and immune responses of shabout.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMohammadian et al. \u003cspan citationid=\"CR150\" class=\"CitationRef\"\u003e2021\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-glucan, MOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAtlantic cod\u003c/p\u003e \u003cp\u003e(\u003cem\u003eGadus morhua\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 g/kg diet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBoth mannan oligosaccharides and β-glucans enhanced Atlantic cod's ability to respond to \u003cem\u003eV. anguillarum\u003c/em\u003e infection.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLokesh et al. \u003cspan citationid=\"CR133\" class=\"CitationRef\"\u003e2012\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMOS\u003c/p\u003e \u003cp\u003e\u003cem\u003eB. subtilis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNile tilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. niloticus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 g /kg\u0026thinsp;\u0026minus;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThe combined treatment positively influenced intestinal morphometry and carcass composition in Nile tilapia.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAzevedo et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2016\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-glucan\u003c/p\u003e \u003cp\u003eAspergillus oryzae (ASP)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNile tilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO.niloticus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5/ 1 g kg\u0026thinsp;\u0026minus;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEnhanced immune responses in tilapia, with pronounced modulation of hematocrit, hemoglobin, RBC, WBC, total protein, and digestive enzyme activities, reaching peak levels in the synbiotic-treated group.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDawood et al. \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e2020\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMOS \u0026amp; Bacillus subtilis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndian Major Carp\u003c/p\u003e \u003cp\u003e(\u003cem\u003eCirrhinus mrigala\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEnhancing innate immunity and disease resistance of \u003cem\u003eC. mrigala\u003c/em\u003e against \u003cem\u003eA. hydrophila\u003c/em\u003e infection.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKumar et al. \u003cspan citationid=\"CR120\" class=\"CitationRef\"\u003e2018\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGOS \u0026amp; Pediococcus acidilactici\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCommon carp\u003c/p\u003e \u003cp\u003e(\u003cem\u003eC. carpio\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGOS 10 g kg\u0026thinsp;\u0026minus;\u0026thinsp;1\u0026thinsp;+\u0026thinsp;P. acidilactici 1 g\u003c/p\u003e \u003cp\u003ekg\u0026thinsp;\u0026minus;\u0026thinsp;1 [0.9 \u0026times; 107 CFU] lyophilized\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 weeks,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eExerted positive effects on selected mucosal and serum immune parameters.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eModanloo et al. \u003cspan citationid=\"CR149\" class=\"CitationRef\"\u003e2017\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGOS\u003c/p\u003e \u003cp\u003e\u003cem\u003eB. subtilis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eL. rohita\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGOS 1 g kg\u0026thinsp;\u0026minus;\u0026thinsp;1\u0026thinsp;+\u0026thinsp;B. subtilis 1 g kg\u0026thinsp;\u0026minus;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 weeks,\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eElicited earlier antioxidant activation, enhanced innate and adaptive immune responses, modulation of immune-related cytokine gene expression, and improved disease resistance.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDevi et al. \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eRecent studies further reinforce the disease-mitigating potential of synbiotics under Bangladeshi aquaculture conditions. Islam et al. (\u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) demonstrated that dietary synbiotics significantly improved growth performance, gut morphology, liver health, and muscle development in Gangetic mystus (\u003cem\u003eMystus cavasius\u003c/em\u003e), with an optimal inclusion level. Importantly, synbiotic-fed fish exhibited elevated red and white blood cell counts, increased neutrophil and lymphocyte populations, and complete survival following challenge with \u003cem\u003eAeromonas veronii\u003c/em\u003e, underscoring their strong immunoprotective capacity and suitability as antibiotic-free disease management tools.\u003c/p\u003e \u003cp\u003eOverall, prebiotics and synbiotics represent promising functional feed additives for promoting gut health, immune competence, and disease resistance in aquaculture species. While laboratory and controlled feeding trials in Bangladesh demonstrate clear benefits, however, evidence of large-scale adoption at the farm level remains limited. Future research should prioritize long-term field validation, cost\u0026ndash;benefit analyses, and species-specific optimization to facilitate the broader integration of prebiotic and synbiotic strategies into sustainable aquaculture health management systems in Bangladesh.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003cdiv class=\"Heading\"\u003e5.1.4 Nanoparticles\u003c/div\u003e \u003cp\u003eNanoparticles (NPs) possess unique physicochemical properties due to their nanoscale size and high surface-area-to-volume ratio, enabling enhanced antimicrobial activity and targeted applications in aquaculture, including feed-based delivery systems, water disinfection, and antimicrobial surface coatings in culture facilities. One of the primary antimicrobial mechanisms of NPs involves direct disruption of bacterial cell membranes. Because bacterial cell surfaces are typically negatively charged, nanoparticles, particularly those with cationic properties, can electrostatically bind to the cell wall depending on surface chemistry and water matrix, destabilizing the membrane, increasing permeability, and ultimately causing cell lysis. Certain nanoparticles, such as graphene oxide, exert physical membrane damage of bacterial, whereas others, including silver nanoparticles (AgNPs), chemically alter membrane integrity through ion release and oxidative stress (Mahmud and Haque, \u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). These mechanisms are effective against both Gram-positive and Gram-negative bacteria and are less prone to resistance development, as they do not rely on specific biochemical targets (Wang et al., \u003cspan citationid=\"CR233\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Godoy et al., 2021). Recent studies suggest that nanoparticles could play a promising role in aquaculture disease management by complementing or enhancing conventional control strategies (Dube, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Abinaya et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Kaul et al., \u003cspan citationid=\"CR107\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Various nanoparticles, including silver (Ag-NPs), gold (Au-NPs), zinc oxide (ZnO-NPs), and titanium dioxide (TiO₂-NPs), have demonstrated strong antimicrobial activity against a wide range of aquatic pathogens (Mahmud and Haque, \u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Ahmed et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Aly et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Cheng et al., \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2009\u003c/span\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). For instance, ZnO-NPs have been shown to inhibit multiple bacterial and fungal pathogens, such as \u003cem\u003eAeromonas hydrophila\u003c/em\u003e, \u003cem\u003eEdwardsiella tarda\u003c/em\u003e, \u003cem\u003eFlavobacterium branchiophilum\u003c/em\u003e, \u003cem\u003eCitrobacter\u003c/em\u003e spp., \u003cem\u003eStaphylococcus aureus\u003c/em\u003e, \u003cem\u003eVibrio\u003c/em\u003e spp., \u003cem\u003eBacillus cereus\u003c/em\u003e, and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (Swain et al., \u003cspan citationid=\"CR217\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). AgNPs are particularly effective due to their ability to release Ag⁺ ions, which bind to membrane proteins, disrupt cellular respiration, and induce bacterial cell death (Lara et al., \u003cspan citationid=\"CR122\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). To enhance biosafety and sustainability, increasing attention has been given to biologically synthesized nanoparticles using medicinal plants, algae, and microbial sources (Mahanty et al., \u003cspan citationid=\"CR138\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Vaseeharan et al. (\u003cspan citationid=\"CR229\" class=\"CitationRef\"\u003e2010\u003c/span\u003e) reported reduced mortality in juvenile shrimp (\u003cem\u003eFenneropenaeus indicus\u003c/em\u003e) infected with \u003cem\u003eVibrio harveyi\u003c/em\u003e following long-term administration of AgNPs synthesized from \u003cem\u003eCamellia sinensis\u003c/em\u003e leaves. Similarly, biogenic AgNPs derived from \u003cem\u003eCaulerpa racemosa\u003c/em\u003e effectively prevented \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e infection in tilapia (Thanigaivel et al., \u003cspan citationid=\"CR224\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). AgNPs biosynthesized by \u003cem\u003ePhormidium formosum\u003c/em\u003e also showed strong antimicrobial efficacy against fish pathogens (Elkomy, \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Furthermore, plant-mediated AgNPs synthesized from \u003cem\u003eOriganum vulgare\u003c/em\u003e leaves were reported to be safer and more effective than chemically produced AgNPs, exhibiting dose-dependent inhibition of bacterial pathogens (\u003cem\u003eStreptococcus agalactiae\u003c/em\u003e, \u003cem\u003eAeromonas hydrophila\u003c/em\u003e, \u003cem\u003eVibrio alginolyticus\u003c/em\u003e) and fungal pathogens (\u003cem\u003eAspergillus flavus\u003c/em\u003e, \u003cem\u003eFusarium moniliforme\u003c/em\u003e, \u003cem\u003eCandida albicans\u003c/em\u003e) (Ghetas et al., \u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Mani et al. (\u003cspan citationid=\"CR142\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) further demonstrated that AgNPs synthesized from \u003cem\u003ePersea americana\u003c/em\u003e pulp exhibited strong antibacterial activity against \u003cem\u003eProvidencia vermicola\u003c/em\u003e infections in rohu. In addition, green-synthesized selenium nanoparticles (SeNPs) from \u003cem\u003eBlumea axillaris\u003c/em\u003e were shown to effectively combat multidrug-resistant aquatic pathogens, offering an alternative to conventional antibiotics (Dash et al., \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). The multimechanistic mode of action of nanoparticles, including membrane disruption, oxidative stress induction, and interference with cellular metabolism, provides a major advantage over traditional antibiotics, as it may reduce the likelihood of resistance development (Xu et al., \u003cspan citationid=\"CR238\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Zhu et al., \u003cspan citationid=\"CR250\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). In Bangladesh, the application of nanoparticle-based approaches in aquaculture remains at an early stage and is largely confined to experimental and nutritional interventions (Bashar et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Ahmed et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2026\u003c/span\u003e) rather than direct medical or therapeutic disease management. Existing studies primarily demonstrate the role of nanoparticles as functional feed additives that enhance growth performance, feed efficiency, and physiological condition, rather than as substitutes for antibiotics in clinical disease treatment. For instance, Bashar et al. (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) reported that dietary supplementation of silica nanoparticles at an optimal level (2 mg kg⁻\u0026sup1; feed) significantly improved growth, feed utilization, and intestinal morphology of Nile tilapia (\u003cem\u003eOreochromis niloticus\u003c/em\u003e) without compromising food safety. Similarly, Ahmed et al. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2026\u003c/span\u003e) showed that selenium nanoparticles (SeNPs), particularly at 1.0 mg kg⁻\u0026sup1; feed, markedly enhanced growth performance, survival, and skeletal development of Asian seabass (\u003cem\u003eLates calcarifer\u003c/em\u003e) broodfish reared under recirculatory aquaculture systems, highlighting their value as functional nano-feed additives. Hasan et al. (\u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) further demonstrated that biosynthesized zinc oxide nanoparticles (ZnONPs) improved growth performance, feed efficiency, and survival of striped dwarf catfish (\u003cem\u003eMystus vittatus\u003c/em\u003e), with biologically meaningful benefits observed at 110 mg kg⁻\u0026sup1; feed and no adverse hematological effects. Despite these promising outcomes, nanoparticle applications in Bangladesh have not yet progressed toward therapeutic or farm-level disease control strategies. Adoption is constrained by limited regulatory frameworks, uncertainties regarding environmental fate and food safety, high production costs, and low farmer awareness (Ahmed et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2026\u003c/span\u003e). Nevertheless, given the country\u0026rsquo;s heavy dependence on antibiotics and the escalating challenge of antimicrobial resistance, green-synthesized and biologically derived nanoparticles hold considerable promise as complementary tools. Future research should prioritize locally sourced nanoformulations, species-specific safety assessments, and field-level validation, alongside standardized toxicity endpoints for cultured fish and non-target aquatic organisms, evaluation of nanoparticle residue accumulation in pond sediments, and potential AMR co-selection risks, to support the responsible integration of nanoparticle-based solutions into sustainable aquaculture health management in Bangladesh.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNanoparticles used in aquaculture health management\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNanoparticle\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHost Species\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTarget pathogen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDoses\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReported effects\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReferences\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAg NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShrimp\u003c/p\u003e \u003cp\u003e\u003cem\u003e(L. vannamei)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. harveyi\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAgNPs reduced bacterial growth to undetectable levels after 4 h of contact, and after 6 h of incubation, almost all treated bacterial cells were dead.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNafisi et al. 2017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u0026nbsp;NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. mossambicus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eB. subtilis\u003c/em\u003e,\u0026nbsp;\u003cem\u003eS. aureus\u003c/em\u003e,\u0026nbsp;\u003cem\u003eE. coli\u003c/em\u003e, and\u0026nbsp;\u003cem\u003eP. aeruginosa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u0026nbsp;mg/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduced the toxic effect and improved the hematological and immunological parameters.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSheta et al., \u003cspan citationid=\"CR203\" class=\"CitationRef\"\u003e2024\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAu NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eShrimp\u003c/p\u003e \u003cp\u003e(\u003cem\u003eL. vannamei\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. parahaemolyticus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 \u0026micro;g/g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHistopathological damage was reduced, immune parameters were enhanced, and survival increased to 80% in shrimp challenged with \u003cem\u003eV. parahaemolyticus\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTello et al. 2019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAu NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. mossambicus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100\u0026nbsp;\u0026micro;g/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEffectively inhibited \u003cem\u003eAeromonas hydrophila\u003c/em\u003e, reduced mortality in infected tilapia, and significantly improved survival and recovery from bacterial infection in \u003cem\u003eO. mossambicus\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVijayakumar et al., \u003cspan citationid=\"CR230\" class=\"CitationRef\"\u003e2017\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZnO NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eTilapia\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. mossambicus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u0026nbsp;and\u0026nbsp;\u003cem\u003eV. parahaemolyticus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2, 5, and 10 mg/g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduced mortality and enhanced disease resistance of \u003cem\u003eA. hydrophila\u003c/em\u003e and \u003cem\u003eV. parahaemolyticus\u003c/em\u003e. Fish receiving this diet showed the highest post-challenge survival, indicating a strong immunostimulatory effect.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbinaya et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2023\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZnO and Se NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRohu\u003c/p\u003e \u003cp\u003e\u003cem\u003e(L. rohita\u003c/em\u003e)\u003c/p\u003e\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eZnO (10 mg/kg) and Se (0.3 mg/kg of feed)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRelative percentage survival (RPS) was significantly higher in the treated groups, accompanied by marked improvements in growth performance and non-specific immune responses, including respiratory burst, lysozyme, and myeloperoxidase activities, compared with the control group.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSwain et al., \u003cspan citationid=\"CR216\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSe NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ePenaeus vannamei\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. harveyi\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHad a good antibacterial activity against\u0026nbsp;\u003cem\u003eV. harveyi\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMansouri-Tehrani et al., \u003cspan citationid=\"CR144\" class=\"CitationRef\"\u003e2021\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMgO NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eM. rosenbergii\u003c/em\u003e PL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100\u0026ndash;500 mg kg\u0026thinsp;\u0026minus;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGeneral health and non-specific immunity were improved.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSrinivasan et al. \u003cspan citationid=\"CR210\" class=\"CitationRef\"\u003e2017\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAg NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eCyprinus carpio\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eF. johnsoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 \u0026micro;g ml-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMortality rate decreased significantly.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eShaalan et al. \u003cspan citationid=\"CR197\" class=\"CitationRef\"\u003e2020\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAg NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eLabeo rohita\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10,15, and 20 \u0026micro;gKg\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTreatment resulted in high survivability, enhanced metabolic activity, improved growth performance, increased immune responses, and effective protection against \u003cem\u003eA. hydrophila\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePopoola et al. \u003cspan citationid=\"CR175\" class=\"CitationRef\"\u003e2023\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChitosan (C)\u0026nbsp;NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. niloticus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5,1 and 2g/kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSerum lysozyme, alternative complement, myeloperoxidase activities, and immunoglobulin M levels were significantly elevated, with the highest survival rate observed in fish fed 2 g/kg when challenged with \u003cem\u003eA. hydrophila\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIbrahim et al. \u003cspan citationid=\"CR99\" class=\"CitationRef\"\u003e2021\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC NPs\u003c/p\u003e \u003cp\u003eAg NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. niloticus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP. fluorescence\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0 g CNPs/kg and 1.0 mg AgNPs/kg diet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBoth CNPs- and AgNPs-treated groups exhibited enhanced non-specific immune parameters and effective defense against \u003cem\u003eP. fluorescens\u003c/em\u003e, with significantly reduced post-infection mortality.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAly et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2023\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAg NPs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e(\u003cem\u003eO. niloticus\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. veronii\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100, 250, 500, and 750\u0026nbsp;\u0026micro;g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAgNP treatment enhanced fish survival and improved hematological, immunological, and antioxidant responses while optimizing liver and kidney function, with the most favorable effects observed at 750 \u0026micro;g/L.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eElgendy et al. \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e2022\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003cdiv class=\"Heading\"\u003e5.1.5 Immunostimulatory Agents\u003c/div\u003e \u003cp\u003eImmunostimulatory agents have attracted considerable attention in healthcare and aquaculture and represent one of the widely investigated areas of applied biomedical and veterinary research. These agents enhance the host\u0026rsquo;s defense capacity by stimulating innate and, in some cases, adaptive immune responses, thereby increasing resistance to infectious diseases. Immunostimulants evaluated in fish health research can be functionally grouped into nutritional additives, microbial-derived products, phytogenic extracts, and synthetic immunomodulators. Of these, nutritional and phytogenic interventions, together with selected microbial derivatives, have gained practical relevance in aquaculture, whereas hormonal agents and several synthetic compounds remain largely restricted to experimental validation (Dawood et al., \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Wang et al., \u003cspan citationid=\"CR233\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Mohapatra et al., \u003cspan citationid=\"CR152\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Meena et al., \u003cspan citationid=\"CR146\" class=\"CitationRef\"\u003e2013\u003c/span\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). In aquaculture, immunostimulatory agents function primarily as prophylactic interventions rather than therapeutic treatments and are most effective when administered before disease onset. Immunostimulants enhance disease resistance in fish primarily by activating key components of the innate immune system, including stimulation of leukocyte activity, increased phagocytosis and bactericidal responses, activation of the complement pathway, and elevated lysozyme and immunoglobulin levels; however, as they generally do not induce antigen-specific immunological memory, the resulting protection is typically short-term (Selvaraj et al., \u003cspan citationid=\"CR195\" class=\"CitationRef\"\u003e2005\u003c/span\u003e; Akbar et al., 2022; Mokhtar et al., \u003cspan citationid=\"CR153\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Due to their non-toxicity, having lower residue concerns than antibiotics, and minimal sensitivity to environmental conditions, immunostimulants are particularly suitable for application during the larval and juvenile stages of fish and shellfish.\u003c/p\u003e \u003cp\u003eHistorically, adjuvants such as Freund\u0026rsquo;s Complete Adjuvant (FCA) were among the earliest immunostimulatory agents used in animals and were successfully applied alongside fish bacterins to enhance immune responses (Mastan, \u003cspan citationid=\"CR145\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Over time, a variety of pathogens affecting aquaculture species have been successfully managed through immunostimulant-based approaches, including bacterial pathogens (\u003cem\u003eAeromonas salmonicida\u003c/em\u003e, \u003cem\u003eA. hydrophila\u003c/em\u003e, \u003cem\u003eVibrio anguillarum\u003c/em\u003e, \u003cem\u003eV. vulnificus\u003c/em\u003e, \u003cem\u003eYersinia ruckeri\u003c/em\u003e, \u003cem\u003eStreptococcus\u003c/em\u003e spp.), viral agents causing infectious hematopoietic necrosis, viral hemorrhagic septicemia, yellow head disease, and parasitic infections such as \u003cem\u003eIchthyophthirius multifiliis\u003c/em\u003e (Barman et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Among immunostimulants, β-glucans are the most extensively studied and widely applied in aquaculture. These polysaccharides, primarily derived from yeast and fungal cell walls, have demonstrated strong immunomodulatory effects in numerous aquatic species, including red sea bream (\u003cem\u003ePagrus major\u003c/em\u003e) (Dawood et al., \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2015\u003c/span\u003eb), rainbow trout (\u003cem\u003eOncorhynchus mykiss\u003c/em\u003e) (Lauridsen \u0026amp; Buchmann, \u003cspan citationid=\"CR123\" class=\"CitationRef\"\u003e2010\u003c/span\u003e), rohu (\u003cem\u003eLabeo rohita\u003c/em\u003e) (Misra et al., \u003cspan citationid=\"CR148\" class=\"CitationRef\"\u003e2006\u003c/span\u003e), koi carp (\u003cem\u003eCyprinus carpio koi\u003c/em\u003e) (Lin et al., \u003cspan citationid=\"CR130\" class=\"CitationRef\"\u003e2011\u003c/span\u003e), and mirror carp (\u003cem\u003eC. carpio\u003c/em\u003e) (Kuhlwein et al., \u003cspan citationid=\"CR118\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). β-glucans enhance phagocytic activity, respiratory burst, and disease resistance, making them reliable immunostimulatory feed additives (Dawood \u0026amp; Koshio, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Other naturally derived polysaccharides, such as fucoidan, a sulfated polysaccharide found in brown seaweeds, have also demonstrated strong immunomodulatory and disease-resistance properties in farmed aquatic species (Prabu et al., \u003cspan citationid=\"CR177\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Isnansetyo et al., \u003cspan citationid=\"CR102\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Immanuel et al., \u003cspan citationid=\"CR100\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Song et al. (\u003cspan citationid=\"CR207\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) reported enhanced antibody (IgM) secretion and improved disease resistance against \u003cem\u003eAeromonas veronii\u003c/em\u003e in crucian carp following supplementation with glucans and Astragalus polysaccharides used as vaccine adjuvants. Similarly, alginate-based compounds have shown promising health benefits; for example, dietary sodium alginate supplementation (0.5%) alleviated high-carbohydrate\u0026ndash;diet-induced liver damage and intestinal dysbiosis in \u003cem\u003eMonopterus albus\u003c/em\u003e, improving metabolic health and gut microbial balance (Zhu et al., \u003cspan citationid=\"CR250\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition to polysaccharide-based immunostimulants, plant-derived phytobiotics play a significant role within the broader category of immunostimulatory agents. Phytobiotics are obtained from various plant parts and contain bioactive compounds such as phenolics, terpenes, organosulfur compounds, alkaloids, phytosterols, saponins, and polysaccharides (Rachwał et al., 2025). These compounds exhibit antimicrobial, antioxidant, anti-inflammatory, and immunostimulatory activities, making them highly valuable for the management of aquaculture health (Sutili et al., \u003cspan citationid=\"CR215\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Abdel-Latif et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eImmunostimulants used in fish species and their reported effects against pathogens\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmuno stimulants\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpecies\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePathogen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDoses\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReported effects\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReferences\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevamisole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRainbow trout\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. mykiss)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eYersinia ruckeri\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,10, 25 \u0026micro;g/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncrease resistance to infection and higher survivability.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIspir, \u003cspan citationid=\"CR103\" class=\"CitationRef\"\u003e2009\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacterial Lipopolysaccharide (LPS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRainbow trout\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. mykiss)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.75, 7.5, and 15 mg/100 g feed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLPS exerted a powerful oxidative burst effect and was a potent mediator of phagocytic, lysozyme, bactericidal, and antiprotease activities.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNya and Austin, \u003cspan citationid=\"CR167\" class=\"CitationRef\"\u003e2010\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-glucan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCommon carp\u003c/p\u003e \u003cp\u003e\u003cem\u003e(C. carpio)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100\u0026ndash;1000 \u0026micro;g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSignificant increase in total blood leucocyte counts and an increase in the proportion of neutrophils and monocytes.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSelvaraj et al. \u003cspan citationid=\"CR195\" class=\"CitationRef\"\u003e2005\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePolygonum minus\u003c/em\u003e extracts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRainbow trout\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. mykiss)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eYersinia ruckeri\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5, 10, and 15 mg/kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBlood\u0026nbsp;lysozyme\u0026nbsp;activity and total\u0026nbsp;Ig\u0026nbsp;showed significantly higher levels. The relative immune gene expressions were upregulated relatively in fish fed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdel et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2020\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack seed (\u003cem\u003eNigella sativa\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGilthead sea bream\u003c/p\u003e \u003cp\u003e\u003cem\u003e(S. aurata)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. harveyi\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBasal diet with 2% \u003cem\u003eN. sativa\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSignificant rise in erythrogram (RBCs, HB, and PCV %), leucogram (total differential leucocytic count), serum total protein, and globulin. Enhance non-specific immunity and minimize susceptibility and pathogenicity to\u0026nbsp;\u003cem\u003eV. harveyi\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAly et al. 2024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEssential oils of clove basil (\u003cem\u003eOcimum gratissimum\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. niloticus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. agalactiae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5, 1.0% and 1.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eImproved intestinal morphology in infected fish.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBrum et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2018\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTurmeric powder (\u003cem\u003eCurcuma\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eLonga)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCommon carp (\u003cem\u003eC. carpio)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0, 2.0, or 5.0 g\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEnhance innate immunity, and prevent common carp aermoniosis at a level of 2.0 g/kg diet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAbdel-Tawwab et al. 2017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTurmeric\u003c/p\u003e \u003cp\u003e\u003cem\u003e(C. longa)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRainbow trout\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. mykiss)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. salmonicida\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0, 1, 2, and 4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHematological values, immune responses, antioxidant capacity, and disease resistance were significantly enhanced.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYonar et al. \u003cspan citationid=\"CR243\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVelvet bean\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Mucuna pruriens)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMossambicus\u003c/p\u003e \u003cp\u003etilapia\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O.\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eMossambicus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0, 2, 4, and\u003c/p\u003e \u003cp\u003e6 g /kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInnate immunity and disease resistance against \u003cem\u003eA. hydrophila\u003c/em\u003e were positively enhanced.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMusthafa et al. \u003cspan citationid=\"CR162\" class=\"CitationRef\"\u003e2018\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAshwagandha\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Withania somnifera)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. niloticus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0, 2.5%, and 5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAntioxidant enzyme activities, including catalase (CAT), glutathione S-transferase (GST), glutathione (GSH), and superoxide dismutase (SOD), were enhanced in liver and muscle, while glutathione peroxidase (GPx) in muscle and serum total antioxidant capacity (TAC) increased significantly.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eZahran et al. \u003cspan citationid=\"CR247\" class=\"CitationRef\"\u003e2018\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSalvadora persica\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. niloticus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0.5,1,2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAntioxidant enzyme activities increased significantly, accompanied by improved hematological and immunological parameters and enhanced survival.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEl-latif et al. 2021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThai ginseng\u003c/p\u003e \u003cp\u003e\u003cem\u003eBoesenbergia rotunda\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. niloticus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. agalactiae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0, 5,10, 20, 40 g TG kg\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLysozyme and peroxidase activities in tilapia skin mucus were significantly enhanced, along with increased serum lysozyme and peroxidase levels, phagocytic index, and respiratory burst activity, resulting in significantly improved disease resistance.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVan Doan et al. \u003cspan citationid=\"CR227\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAssam tea\u003c/p\u003e \u003cp\u003e\u003cem\u003eCamellia sinensis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. niloticus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. agalactiae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0, 1, 2, 4, and 8 g kg\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEnhanced humoral and mucosal immunity, improved growth performance, and conferred greater resistance against \u003cem\u003eS. agalactiae.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eVan Doan et al., \u003cspan citationid=\"CR227\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eTrigonella foenum-graecum\u003c/em\u003e (Fenugreek)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCommon Carp (\u003cem\u003eC. carpio\u003c/em\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5,1,5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTreated fish showed significant increases in erythrocytes, leukocytes, hematocrit, and hemoglobin, resulting in enhanced immunity of \u003cem\u003eCyprinus carpio\u003c/em\u003e against \u003cem\u003eA. hydrophila\u003c/em\u003e infection.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSyeed et al., \u003cspan citationid=\"CR218\" class=\"CitationRef\"\u003e2018\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLemon Peel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eO. niloticus\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eClarias gariepinus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hyrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1%, 2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSerum lysozyme activity, myeloperoxidase levels, and phagocytic activity increased in both fish species, accompanied by improved enzymatic antioxidant capacity and immune responses.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRahman et al. \u003cspan citationid=\"CR180\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAchyranthes aspera\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRohu\u003c/p\u003e \u003cp\u003e\u003cem\u003e(L. rohita)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGrowth performance, immune enzyme activities, and the expression of key immune-related genes in rohu were significantly enhanced, while oxidative stress was reduced.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKumar et al. \u003cspan citationid=\"CR119\" class=\"CitationRef\"\u003e2019\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurcumin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCommon carp\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Ctenopharyngodon idella)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eA. hydrophila\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0, 196.11, 393.67, 591.46, and 788.52 mg/kg diet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncreased lysozyme (LYZ) and acid phosphatase (ACP) activities, elevated complement C3 and C4 levels, and reduced alanine aminotransferase activity, thereby enhancing disease resistance, innate immunity, and antioxidant capacity while attenuating inflammatory responses in fish.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMing et al. \u003cspan citationid=\"CR147\" class=\"CitationRef\"\u003e2020\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGinger\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Zingiber officinale)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAsian sea bass\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Lates calcarifer)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV. harveyi\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1, 2, 3, 5, and 10 g/kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInfluenced hematological, biochemical, and immunological parameters, with elevated erythrocyte (RBC) and leukocyte (WBC) counts, thereby strengthening nonspecific immunity and reducing susceptibility to \u003cem\u003eV. harveyi\u003c/em\u003e.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTalpur et al. \u003cspan citationid=\"CR220\" class=\"CitationRef\"\u003e2013\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAloe vera\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTilapia\u003c/p\u003e \u003cp\u003e\u003cem\u003e(O. niloticus)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eS. iniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1% and 2%/kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncreases in red blood cells, hematocrit, hemoglobin, white blood cells, neutrophils, monocytes, eosinophils, serum total protein, and glucose, and no mortality was recorded following the challenge test.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGabriel et al., \u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e2015\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGuava leaf extract\u003c/p\u003e \u003cp\u003e\u003cem\u003e(Psidium guajava)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhite shrimp (\u003cem\u003eP. vannamei)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eV parahaemolyticus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0, 1, 5, and 10 g kg\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eResistance to \u003cem\u003eV. parahaemolyticus\u003c/em\u003e was significantly enhanced, with a survival rate of 72.27% and an effective stimulation of the nonspecific immune response.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDewi et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2021\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNumerous studies have demonstrated that phytobiotics enhance both innate and adaptive immune responses, thereby improving disease resistance and may reduce the need for antibiotics (Awad and Awad, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Abdul Kari et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Beyond immune enhancement, phytobiotics contribute to environmental sustainability by degrading naturally and posing minimal ecological risks compared to synthetic chemicals (Bhanja et al., \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Organ-level benefits have also been reported, including reduced renal necrosis and inflammation, improved hepatic structure, better lipid metabolism, and enhanced intestinal morphology (Tan et al., \u003cspan citationid=\"CR221\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). For example, dietary supplementation with \u003cem\u003ePsidium guajava\u003c/em\u003e leaf extract increased intestinal surface area and nutrient absorption in \u003cem\u003eOreochromis niloticus\u003c/em\u003e, thereby improving growth and health status (Omitoyin et al., \u003cspan citationid=\"CR169\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Garlic (\u003cem\u003eAllium sativum\u003c/em\u003e) supplementation has similarly been shown to enhance growth performance, physiological condition, and disease resistance in rohu (\u003cem\u003eLabeo rohita\u003c/em\u003e) and African catfish (\u003cem\u003eClarias gariepinus\u003c/em\u003e) (Sahu et al., \u003cspan citationid=\"CR188\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Thanikachalam et al., \u003cspan citationid=\"CR225\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). In Bangladesh, the practical application of immunostimulants in aquaculture remains relatively limited and uneven, despite growing experimental evidence supporting their benefits in worldwide. Studies conducted under local farming conditions have demonstrated that plant-derived additives and herbal formulations can enhance growth performance, innate immune responses, and resistance to bacterial pathogens in major cultured species such as carp, tilapia, and pangasius (Faruk et al., \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e2021\u003c/span\u003ea). However, widespread farm-level adoption is constrained by inadequate standardization of dosage protocols, variability in raw material quality, limited availability of validated commercial products, and insufficient extension support for farmers (Sarker et al., \u003cspan citationid=\"CR194\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). These challenges are further compounded by the dominance of antibiotics as a rapid-response disease management tool in many production systems. Nevertheless, increasing global emphasis on antimicrobial stewardship, residue-free aquaculture products, and environmentally sustainable production practices is expected to accelerate the interest in functional feed additives, including immunostimulants. In this context, Bangladesh presents significant opportunities for the development of locally adapted, low-cost botanical immunostimulant strategies aligned with circular bioeconomy principles and climate-resilient aquaculture frameworks. Strengthening collaborative research, establishing regulatory quality standards, and conducting large-scale participatory field validation will be crucial to bridge the gap between experimental success and commercial adoption. Ultimately, integrating immunostimulant-based health management approaches within broader global efforts to reduce antibiotic dependency can contribute to safer aquatic food systems, improved farmer livelihoods, and enhanced ecosystem sustainability.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003cdiv class=\"Heading\"\u003e5.1.6 Quorum Quenching\u003c/div\u003e \u003cp\u003eBacteria communicate through quorum sensing (QS), a cell-density-dependent signaling system that regulates collective behaviors such as virulence factor production, motility, and biofilm formation. This communication relies on the synthesis, release, and detection of extracellular signaling molecules, enabling bacteria to coordinate pathogenicity and environmental adaptation (Yi et al., \u003cspan citationid=\"CR242\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Zhong et al., 2021). In aquaculture, several major pathogens, including members of the Vibrionaceae family and the genera Vibrio, Aeromonas, and Pseudomonas, use QS systems to regulate virulence traits that are critical for host colonization and disease progression (Gupta et al., 2022). QS-regulated behaviors, such as flagellated swarming motility, further enhance pathogenicity in some pathogens and promote biofilm formation, increasing resistance to host defenses and conventional antibiotics (Muduli et al., \u003cspan citationid=\"CR156\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Li et al., \u003cspan citationid=\"CR128\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Quorum quenching (QQ), which disrupts bacterial communication without killing the pathogen, has emerged as a promising complementary to antibiotics. Unlike conventional antimicrobials, QQ strategies may reduce bactericidal selection pressure and potentially lower resistance selection compared with antibiotics. A wide range of anti-QS compounds including plant-derived molecules such as cinnamaldehyde, eugenol, quercetin, coumaric acid, limonoids, and ajoene have been shown to inhibit QS-regulated pathogenicity across multiple bacterial species (Jakobsen et al., \u003cspan citationid=\"CR104\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Asfour et al., 2018; Topa et al., \u003cspan citationid=\"CR226\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Ribeiro et al., \u003cspan citationid=\"CR183\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Shastri et al., \u003cspan citationid=\"CR202\" class=\"CitationRef\"\u003e2025\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMultiple studies suggest the effectiveness of QQ-producing microorganisms as biocontrol agents in aquaculture (Lubis et al., \u003cspan citationid=\"CR135\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Khatimah et al., \u003cspan citationid=\"CR111\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Multiple studies have demonstrated that \u003cem\u003eBacillus\u003c/em\u003e spp. possess intrinsic QQ activity through enzymatic degradation of N-acyl homoserine lactone (AHL) signals. For example, AHL-degrading \u003cem\u003eBacillus\u003c/em\u003e strains significantly suppressed virulence gene expression, swarming motility, and biofilm formation in \u003cem\u003eVibrio harveyi\u003c/em\u003e, resulting in enhanced survival of shrimp post-larvae challenged with luminescent vibriosis (Vinoj et al., \u003cspan citationid=\"CR231\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Shaheer et al., \u003cspan citationid=\"CR198\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Similarly, \u003cem\u003eBacillus licheniformis\u003c/em\u003e strains identified by Chen et al. (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) disrupted AHL-mediated QS in \u003cem\u003eAeromonas hydrophila\u003c/em\u003e, achieving approximately 70% survival in zebrafish challenge assays, with genomic evidence confirming the presence of AHL-degrading enzymes. Recent studies further reinforce these findings. \u003cem\u003eBacillus velezensis\u003c/em\u003e strains have consistently shown strong QQ activity against \u003cem\u003eVibrio\u003c/em\u003e pathogens. Monz\u0026oacute;n-Atienza et al. (\u003cspan citationid=\"CR155\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) reported that \u003cem\u003eB. velezensis\u003c/em\u003e D-18 disrupted QS in \u003cem\u003eVibrio anguillarum\u003c/em\u003e via lactonase activity encoded by the \u003cem\u003eytnP\u003c/em\u003e gene, thereby reducing biofilm formation. Likewise, \u003cem\u003eB. velezensis\u003c/em\u003e DH82 significantly attenuated \u003cem\u003eVibrio parahaemolyticus\u003c/em\u003e virulence, reduced pathogen abundance in shrimp culture systems, and improved host immune responses in \u003cem\u003eLitopenaeus vannamei\u003c/em\u003e (Sun et al., \u003cspan citationid=\"CR214\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). These findings highlight strong agreement on the antivirulence potential of \u003cem\u003eBacillus\u003c/em\u003e-based QQ probiotics. Beyond bacterial probiotics, bioactive compounds from marine and plant sources have also demonstrated QQ efficacy. Saponins extracted from the sea cucumber \u003cem\u003eHolothuria leucospilota\u003c/em\u003e significantly inhibited QS-regulated virulence factors in \u003cem\u003eAeromonas hydrophila\u003c/em\u003e by downregulating key QS genes (\u003cem\u003eahyI\u003c/em\u003e and \u003cem\u003eahyR\u003c/em\u003e), without exerting bactericidal effects (Payam et al., \u003cspan citationid=\"CR171\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Similarly, cyanobacteria-derived phenolic compounds produced by \u003cem\u003eLeptolyngbya\u003c/em\u003e sp. disrupted QS signaling in \u003cem\u003eVibrio harveyi\u003c/em\u003e by suppressing the LuxP receptor, thereby reducing virulence and pathogen load without inhibiting bacterial growth (Saranya et al., \u003cspan citationid=\"CR192\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). These studies collectively support the concept that QQ-based interventions show potential across diverse biological sources.\u003c/p\u003e \u003cp\u003eDespite strong experimental limitations on the efficacy of QQ strategies, their application in aquaculture remains largely confined to laboratory and pilot-scale studies. Disagreements in the literature primarily concern variability in QQ efficacy under complex field conditions, strain specificity, the stability of QQ enzymes in aquatic environments, and challenges associated with large-scale delivery. While in vivo challenge trials consistently demonstrate improved host survival, long-term field validation under commercial farming conditions is still limited.\u003c/p\u003e \u003cp\u003eIn Bangladesh, quorum quenching has not yet been implemented at the farm level, and no commercial QQ-based products are currently in use. Aquaculture disease management in the country remains heavily reliant on antibiotics, despite increasing evidence of antimicrobial resistance. Nevertheless, the feasibility of QQ strategies in Bangladesh is promising, particularly through the use of locally isolated probiotic \u003cem\u003eBacillus\u003c/em\u003e strains and plant- or algae-derived bioactive compounds. QQ approaches are potentially cost-effective, environmentally benign, and compatible with existing probiotic-based management practices. Future research should prioritize isolating native QQ-producing microbes, evaluating their performance under pond-based farming systems, and integrating them with immunostimulatory and probiotic strategies to develop scalable, antibiotic-free disease control solutions for sustainable aquaculture in Bangladesh. Particular attention should also be given to practical delivery considerations, including the stability of QQ enzymes or signalling-disrupting compounds in effective feed-based incorporation methods, and optimization of dosing frequency under field conditions.\u003c/p\u003e \u003c/div\u003e"},{"header":"6. Technology Readiness of Antibiotic Alternatives in Bangladeshi Aquaculture","content":"\u003cp\u003eTo contextualize the experimental evidence presented above, antibiotic alternatives were evaluated using an adapted Technology Readiness Level (TRL) framework reflecting their maturity and adoption status in Bangladeshi aquaculture (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). Technology levels were assigned based on predefined criteria, including the scale of validation (laboratory vs pond), reproducibility of biological outcomes, availability of standardized formulations, and regulatory status. The assessment highlights clear disparities between biological efficacy and real-world application. Probiotics, prebiotics, and synbiotics exhibit relatively greater readiness due to extensive experimental validation and partial farm-level adoption, though primarily as growth and health-promoting additives rather than as a disease prevention tool. In contrast, immunostimulants and phytobiotics with promising experimental outcomes but limited and inconsistent field application. Emerging approaches, such as quorum quenching and nanoparticle-based interventions, are confined largely to laboratory and pilot-scale studies, indicating early readiness and no documented large-scale adoption in Bangladesh.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdapted technology readiness levels (TRL) and adoption status of antibiotic alternatives in Bangladeshi aquaculture\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotic alternative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimary function\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGlobal evidence status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdoption status in Bangladesh\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAdapted TRL*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKey limitations for Bangladesh\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModulation of gut microbiota, immune enhancement, and disease prevention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWidely validated through laboratory, field, and commercial applications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCommercially available; partially adopted, often without regulation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u0026ndash;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLack of strain standardization, inconsistent product quality, and weak regulatory oversight\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrebiotics and Synbiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStimulation of beneficial gut microbes and immune response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStrong experimental and field evidence globally\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLimited and fragmented use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLimited awareness, cost, and formulation challenges\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunostimu-\u003c/p\u003e \u003cp\u003elatory agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEnhancement of innate and adaptive immune responses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProven efficacy in controlled trials and some field applications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLimited use, mostly experimental\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCost, inconsistent responses across species, and limited farmer knowledge\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaccines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTargeted prevention of specific bacterial and viral diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWidely used globally in commercial aquaculture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVery limited use; species- and disease-specific\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh cost, cold-chain requirements, limited local availability\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNanoparticles\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAntimicrobial delivery, immune modulation, pathogen control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUsed globally in commercial farming\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo reported application in the fields at the farmer's level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRegulatory uncertainty, safety concerns, and a lack of field validation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuarum Quensing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDisruption of bacterial communication and virulence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMostly experimental and proof-of-concept studies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo application\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEarly-stage research\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTRL values were adapted to the Bangladeshi aquaculture context based on experimental validation, regulatory readiness, infrastructure availability, and the degree of farm-level adoption, rather than on global technological maturity.\u003c/p\u003e"},{"header":"7. Institutional and Regulatory Challenges in Aquaculture Health and Drug Use","content":"\u003cp\u003eUniversities and higher education institutions play a pivotal role in shaping sustainable aquaculture health management; however, in Bangladesh, this potential appears underutilized. Most fisheries and aquaculture curricula often place limited emphasis on aquatic animal pharmacology, toxicology, antimicrobial stewardship, and rational drug use. Pharmacology-related components are often absent or treated superficially, with minimal practical exposure to disease diagnosis, prescription protocols, withdrawal periods, and mechanisms of antimicrobial resistance. Furthermore, the lack of laboratory-based training in fish disease diagnostics, antimicrobial susceptibility testing, and residue analysis likely constrains graduates' capacity to provide evidence-based health advisory services. Consequently, many aquaculture professionals entering the sector are insufficiently equipped to discourage irrational antibiotic use or to effectively promote alternative disease management strategies.\u003c/p\u003e \u003cp\u003eThese educational shortcomings are compounded by broader structural deficiencies in diagnostic infrastructure. Most aquaculture-producing regions in Bangladesh lack accessible fish health diagnostic laboratories, and pathogen-specific diagnosis prior to treatment is not routinely practiced. In the absence of diagnostic support, antibiotics are routinely applied as empirical remedies, reinforcing misuse and accelerating the development of antimicrobial resistance. Strengthening linkages among universities, research institutes, and extension services, integrating applied pharmacology and fish health diagnostics into academic curricula, and expanding hands-on training opportunities are, therefore, essential for building a technically competent workforce capable of supporting antibiotic-sparing aquaculture.\u003c/p\u003e \u003cp\u003eEconomic and production-system constraints further complicate the implementation of alternative health management strategies. The predominance of small-scale and semi-intensive farming systems limits the practicality of injectable vaccines and advanced diagnostic tools, while the relatively high upfront costs of some alternatives, such as vaccines and nano-feed additives, discourage adoption in the absence of targeted subsidies or incentive mechanisms. In addition, limited public\u0026ndash;private partnerships and insufficient investment in locally driven innovation restrict the development and scaling of Bangladesh-specific solutions, despite the country\u0026rsquo;s rich indigenous plant resources and microbial biodiversity that could support low-cost phytobiotics, probiotics, and green-synthesized nanoparticles.\u003c/p\u003e \u003cp\u003eMarket dynamics further intensify antibiotic dependency. The aquaculture input sector in Bangladesh is characterized by a long and weakly regulated supply chain involving pharmaceutical companies, distributors, dealers, and field-level sales representatives (Ali et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Antibiotics and chemotherapeutics are actively marketed, often bundled with feed and other inputs, and promoted directly to farmers without veterinary oversight. Company representatives have been reported to influence influence disease management decisions, encouraging antibiotic use even in the absence of confirmed bacterial infections. This practice may disproportionately affects small-scale, low-literacy farmers, who often rely on dealer advice because of limited technical knowledge. As a result, in some farmer communities antibiotics may be perceived as routine growth- and survival-enhancing inputs rather than as last-resort therapeutic agents.\u003c/p\u003e \u003cp\u003eAddressing these challenges requires coordinated institutional and policy reform to support the responsible transition toward antibiotic-sparing aquaculture in Bangladesh. Priority actions include strengthening regulatory oversight of aquaculture therapeutics, establishing clear national standards and approval pathways for antibiotic alternatives, and integrating aquaculture more explicitly into national AMR surveillance and broader One Health coordination frameworks. Practical policy instruments, including incentive-based certification schemes for antibiotic-free production, targeted subsidies or credit support for preventive health technologies, and structured capacity-building programs for farmers and extension personnel, could significantly accelerate the adoption of preventive disease management approaches. In parallel, enhanced collaboration among academic and research institutions, regulatory authorities, private feed and pharmaceutical industries, and farmer organizations will be essential to translate laboratory-scale innovations into validated field-level solutions. Without such institutional alignment, regulatory clarity, and sustained investment in knowledge transfer systems, the shift toward sustainable, resilient, and antibiotic-reduced aquaculture production in Bangladesh is likely to remain fragmented and slow, despite strong and growing scientific evidence supporting alternative health management strategies\u003c/p\u003e"},{"header":"8. Conclusion","content":"\u003cp\u003eThis review provides an integrative synthesis of antibiotic use, AMR risks, and the current landscape of antibiotic alternatives in Bangladeshi aquaculture, highlighting both scientific progress and persistent implementation gaps, including insufficient extension support, lack of standardized product evaluation systems, and limited large-scale field adoption. Evidence indicates that the continued reliance on antibiotics, often applied empirically and without proper diagnosis, poses substantial risks to aquatic animal health, environmental integrity, and public health through selection and dissemination of resistant bacteria/genes. Although Bangladesh has made notable advances in aquaculture productivity, health management practices appear not to have evolved at a comparable pace, resulting in a structural dependence on chemotherapeutics. A wide range of antibiotic alternatives, including probiotics, prebiotics, synbiotics, immunostimulants, phytobiotics, vaccines, quorum-quenching strategies, and nanoparticle-based interventions, has strong potential to reduce reliance on antibiotics. Among these, probiotics, prebiotics, and synbiotics exhibit the highest relative readiness, supported by extensive experimental validation and partial farm-level adoption, albeit predominantly as growth- and health-promoting additives rather than antibiotic-sparing disease prevention and control tools. Although immunostimulants, phytobiotics, and vaccines have demonstrated promising biological effectiveness, their broader application remains constrained by insufficient standardization of formulations, dosing protocols, and field validation in Bangladesh. Emerging approaches such as quorum quenching and nanotechnology-based interventions remain at early developmental stages, with evidence largely confined to laboratory and pilot-scale studies and no documented large-scale adoption in Bangladesh. The adapted TRL assessment underscores a substantial disconnect between experimental success and real-world application. This gap is influenced by a lack of scientific evidence, but by institutional, regulatory, economic, and knowledge-based barriers, including inadequate fish health diagnostics, limited pharmacological training, weak regulatory oversight of aquaculture therapeutics, and antibiotic sales from market pressure promotion. The absence of coordinated policy incentives and farmer-centric extension services further hampers the transition toward antibiotic-sparing production systems. Moving forward, a successful reduction in antibiotic dependence will require an integrated strategy that combines science, policy, and practice. Strengthening academic curricula in aquatic pharmacology and disease diagnostics, investing in regional fish health laboratories, regulating antibiotic marketing channels, and reforming national fisheries and AMR-related policies are essential steps. Simultaneously, prioritizing field-level validation, product quality/standardization, cost-effectiveness analysis, and species-specific optimization of antibiotic alternatives will enhance farmer confidence and adoption. With coordinated institutional reform and evidence-based policy support, Bangladesh has a strong opportunity to transition toward sustainable, antibiotic-sparing aquaculture systems that safeguard productivity, environmental health, and food safety.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u0026nbsp;\u003c/strong\u003eNo datasets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Conceptualization, M.N.M., M.M.H., and N.A.H; Methodology, M.N.M. and N.A.H; Data curation, M.N.M., M.M.A and N.A.H; Reviewed the literature, M.N.M., S.S., and M.Z.R.J; Writing original draft, M.N.M., M.M.H., and N.A.H; Writing, review \u0026amp; editing, M.N.M., M.M.H., and N.A.H; Supervision, M.M.H and N.A.H. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e The authors used Grammarly to improve the readability and language of the manuscript. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors disclosed no conflict of interest to anybody or any organization.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAbd El-Latif, A., Ashraf, M., Abd El-Gawad, E. A., Soror, E. I., Shourbela, R. M., \u0026amp; Zahran, E. (2021). 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Probiotics application in aquaculture: Its potential effects, current status in China and future prospects. \u003cem\u003eFrontiers in Marine Science, 11\u003c/em\u003e, 1455905. https://doi.org/10.3389/fmars.2024.1455905\u003c/li\u003e\n \u003cli\u003eRahman, A. N. A., ElHady, M., \u0026amp; Shalaby, S. I. (2019). Efficacy of dehydrated lemon peels on the immunity, enzymatic antioxidant capacity and growth of Nile tilapia (\u003cem\u003eOreochromis niloticus\u003c/em\u003e) and African catfish (\u003cem\u003eClarias gariepinus\u003c/em\u003e). \u003cem\u003eAquaculture, 505\u003c/em\u003e, 92\u0026ndash;97. https://doi.org/10.1016/j.aquaculture.2019.02.051\u003c/li\u003e\n \u003cli\u003eRahman, M. M., Rahman, M. A., Hossain, M. T., Siddique, M. P., Haque, M. E., Khasruzzaman, A. K. M., \u0026amp; Islam, M. A. (2022). 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R., Kamarudin, M. S., Sijam, K., Arshad, A., \u0026amp; Nejat, N. (2012). Effects of \u003cem\u003eBacillus subtilis\u003c/em\u003e on the growth performance, digestive enzymes, immune gene expression and disease resistance of white shrimp, \u003cem\u003eLitopenaeus vannamei\u003c/em\u003e. \u003cem\u003eFish \u0026amp; Shellfish Immunology, 33\u003c/em\u003e(4), 683\u0026ndash;689. https://doi.org/10.1016/j.fsi.2012.05.027\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Antimicrobial resistance (AMR), Antibiotic alternatives, Fish health management, Probiotics and immunostimulants, Sustainable aquaculture","lastPublishedDoi":"10.21203/rs.3.rs-9386222/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9386222/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe rapid expansion of aquaculture in Bangladesh has substantially increased national fish production but has simultaneously intensified dependence on antibiotics for disease prevention and treatment, thereby accelerating the emergence and dissemination of antimicrobial resistance (AMR). This review critically evaluates the current landscape of antibiotic use, AMR prevalence, and the potential of non-antibiotic disease management strategies to foster sustainable and antibiotic-sparing aquaculture systems in Bangladesh. A structured evidence synthesis was conducted following the Joanna Briggs Institute guidance, drawing on peer-reviewed and gray literature published. The synthesis reveals widespread empirical and often unregulated antibiotic application across freshwater and brackish-water systems, accompanied by high frequencies of multidrug-resistant bacterial isolates and detectable antibiotic residues in cultured fish and surrounding environments. These patterns underscore significant risks to food safety, ecosystem integrity, and public health. In contrast, a broad spectrum of alternative approaches, including probiotics, prebiotics, synbiotics, phytobiotics, immunostimulants, vaccines, and nanoparticle-based interventions, demonstrate strong experimental efficacy in enhancing host immunity, modulating gut microbiota, reducing pathogen load, and improving survival and growth metrics. An adapted technology readiness perspective indicates that probiotics and synbiotics possess the highest practical maturity, whereas phytobiotics and immunostimulants show promising but inconsistent field performance, and nanotechnology-based solutions largely remain at pilot or laboratory stages in Bangladesh. The principal barrier to transition is therefore not scientific insufficiency but institutional and policy fragmentation. Strengthening fish health diagnostics, reforming regulatory oversight of aquaculture therapeutics, expanding farmer-centric extension services, and prioritizing field-scale validation and cost\u0026ndash;benefit analyses are essential to reduce antibiotic dependency. Integrating scientific innovation with coordinated policy and capacity development offers Bangladesh a viable pathway toward environmentally sustainable, economically resilient, and public-health-protective aquaculture production.\u003c/p\u003e","manuscriptTitle":"Breaking Antibiotic Dependency in Aquaculture: Evaluating Alternative Disease Management Strategies for Sustainable Aquaculture in Bangladesh","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 14:10:21","doi":"10.21203/rs.3.rs-9386222/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"22db00cf-4833-493f-ad3e-4695cdab7eef","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T20:55:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 14:10:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9386222","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9386222","identity":"rs-9386222","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}