Characteristics and clinical applicability of five dietary interventions for irritable bowel syndrome: a Systematic review and Network meta-analysis

Characteristics and clinical applicability of five dietary interventions for irritable bowel syndrome: a Systematic review and Network meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Characteristics and clinical applicability of five dietary interventions for irritable bowel syndrome: a Systematic review and Network meta-analysis Xinpeng Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9245067/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 Background Dietary interventions are first-line management for irritable bowel syndrome (IBS), but their relative efficacy, acceptability, and safety remain incompletely understood. This systematic review and meta-analysis aimed to comprehensively evaluate five dietary interventions (LFD, MD/MED-LFD, TDA, SSRD, GFD) for adult IBS patients. Methods We searched PubMed, Embase, Cochrane Library, and Web of Science for RCTs published between 2019 and 2025 comparing dietary interventions for IBS. Meta-analyses were performed using a random-effects model, and risk of bias was assessed using the Cochrane RoB 2.0 tool. Results Ten RCTs involving 939 participants were included. Frequentist network meta-analysis demonstrated that all specific dietary interventions were significantly superior to habitual diet/control. Based on the P-score ranking matrix, the combined Mediterranean-low FODMAP diet (MED-LFD) had the highest probability of being the most effective intervention (P-score = 0.76), followed by the starch- and sucrose-reduced diet (SSRD, P-score = 0.70), Mediterranean diet alone (MD, P-score = 0.68), and LFD (P-score = 0.60). Traditional dietary advice (TDA) showed lower comparative efficacy (P-score = 0.20). Node-splitting analysis confirmed the robustness of the network model with no significant local inconsistency (P > 0.05 for all). Conclusion LFD, MED-LFD, TDA, SSRD, and GFD have distinct efficacy, acceptability, and safety profiles. LFD is a reliable first-line option, MED-LFD offers favorable long-term outcomes, TDA is acceptable but less effective, SSRD is a viable alternative to LFD, and GFD is only suitable for specific subgroups. Further research is needed to confirm long-term efficacy and identify subgroup responders. Irritable bowel syndrome Dietary intervention Low FODMAP diet Mediterranean diet Traditional dietary advice Starch and sucrose-reduced diet Gluten-free diet Systematic review Meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Plain Language Summary Irritable bowel syndrome (IBS) is a common gut disorder that causes repeated abdominal pain, bloating, and irregular bowel habits, which can seriously lower quality of life. Dietary changes are the first-choice treatment for people with IBS, but the best diet differs from person to person. This systematic review and meta-analysis summarized evidence from 10 recent high-quality clinical trials comparing five main dietary strategies for IBS: the low FODMAP diet, Mediterranean-style diet, traditional dietary advice based on clinical guidelines, and newer approaches including the starch-sucrose-reduced diet and gluten-free diet. All diets were safe and well-tolerated. The low FODMAP diet provided strong short-term symptom relief, especially for those with diarrhea-predominant IBS. The combined Mediterranean low-FODMAP diet offered steady, long-term benefit. Traditional dietary advice was the simplest and most practical to follow in daily life. The starch-sucrose-reduced diet worked just as well as the low FODMAP diet and was easier for patients to maintain. Effects of the gluten-free diet were inconsistent across studies. Overall, no single diet works best for everyone. We recommend that people with IBS use a personalized approach when choosing a diet, based on their main symptoms, lifestyle, and personal preferences. 1. Introduction Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder defined by recurrent abdominal pain, bloating, and disturbed bowel habits, affecting an estimated 4%–15% of the global population [ 14 ]. Its chronic, relapsing course is closely linked to impaired health-related quality of life, work productivity, and elevated psychological burden, representing a substantial clinical and public health challenge [ 14 ]. While pharmacotherapy remains a mainstay of management, long-term use is often constrained by adverse effects, variable efficacy, and suboptimal patient adherence. In contrast, dietary intervention has emerged as a first-line, guideline-recommended strategy for IBS, favored for its favorable safety profile, clinical effectiveness, and broad accessibility [ 12 , 14 ]. Multiple dietary approaches have been investigated for IBS, including three well-established interventions—the low FODMAP diet (LFD), Mediterranean diet (MD), and National Institute for Health and Care Excellence (NICE)-based traditional dietary advice (TDA)—alongside emerging regimens represented by the starch- and sucrose-reduced diet (SSRD) and gluten-free diet (GFD). The LFD restricts fermentable oligo-, di-, monosaccharides, and polyols to reduce intestinal osmotic stress and microbial fermentation, with moderate-quality evidence supporting its efficacy for global symptom relief, particularly in diarrhea-predominant IBS (IBS-D) [ 12 , 13 ]. The MD, distinguished by high consumption of fruits, vegetables, extra-virgin olive oil, whole grains, and fish, may improve IBS via gut microbiota modulation, anti-inflammatory effects, and enhanced gut-brain axis function, with documented benefits for IBS Symptom Severity Score (IBS-SSS) and IBS-related quality of life (IBS-QOL) [ 13 ]. NICE-based TDA emphasizes regular eating patterns and avoidance of common gut irritants (e.g., high-fat, spicy, caffeinated, or alcoholic foods) and is widely recognized for its high acceptability and low implementation burden [ 9 , 13 ]. Among emerging diets, SSRD targets sucrase-isomaltase insufficiency and has demonstrated non-inferior symptom control relative to LFD, with additional metabolic advantages such as reduced sugar craving and weight management [ 11 ]; GFD may benefit roughly 30% of IBS patients, particularly those with non-celiac gluten sensitivity, but shows inconsistent effects in unselected IBS populations [ 3 , 13 ]. Despite a growing body of randomized controlled trials (RCTs) evaluating these diets individually, critical gaps remain in the current evidence base. First, few studies have performed direct head-to-head comparisons across core clinical domains including efficacy, adherence, and safety [ 9 , 13 ]. Second, substantial clinical and methodological heterogeneity persists across trials, including variations in intervention protocols (e.g., LFD restriction intensity, MD standardization), outcome definitions (e.g., responder criteria), and study populations (e.g., IBS subtype distribution, cultural dietary backgrounds) [ 12 , 13 ]. Such heterogeneity limits formal quantitative synthesis (meta-analysis) of pooled effect estimates and has impeded structured descriptive integration of evidence. As a result, the relative performance, strengths, limitations, and optimal target subgroups of each dietary intervention remain poorly defined. A key methodological feature of this review is the clear conceptual separation between therapeutic intervention trials and mechanistic challenge (provocation) studies. Therapeutic trials evaluate dietary patterns as clinical treatments for IBS, with intervention durations typically ≥ 4 weeks and outcomes focused on clinically meaningful symptom improvement. In contrast, mechanistic challenge studies administer short-term (1–7 days) high-dose dietary components (e.g., FODMAPs, gluten) to probe symptom-triggering mechanisms and causal pathophysiological pathways. Although both study types are included, they serve distinct roles: therapeutic trials form the primary evidence base for assessing clinical efficacy, while challenge studies are used only as supportive mechanistic evidence and are not pooled or directly compared with therapeutic trials in efficacy synthesis. Against this background, the present systematic review summarizes evidence from 10 independent therapeutic RCTs published between 2019 and 2025, with a structured descriptive synthesis of LFD, MD (including MED-LFD), NICE-based TDA, and emerging diets (SSRD, GFD). We systematically evaluate performance across four core domains: clinical efficacy (global response rates, IBS subtype-specific effects, key symptom improvement), acceptability and adherence (implementation difficulty, persistence, patient preference), safety (adverse events, nutritional safety, long-term metabolic effects), and clinical applicability (suitability for IBS subtypes, cultural dietary contexts, and real-world implementation). By clarifying the distinct profiles and practical trade-offs of each intervention within the limits of existing heterogeneity, this review aims to support evidence-based, personalized dietary decision-making for IBS in routine clinical practice. 2. Methods 2.1 Study registration This systematic review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420261335612 2.2 Study selection and eligibility criteria 2.2.1 Study design Eligible studies were full-text, peer-reviewed randomized controlled trials (RCTs), including parallel-group, crossover, and factorial designs. Pilot RCTs were also eligible, provided they reported complete data on the prespecified outcomes (consistent with Section 2.4 ). Non-randomized studies (e.g., cohort studies, case-control studies), case reports, systematic reviews, meta-analyses, letters, comments, conference abstracts, and unpublished data were excluded to minimize bias and ensure the methodological rigor and reliability of the included evidence. 2.2.2 Study population • Participants: Adult patients aged ≥ 18 years with a confirmed diagnosis of irritable bowel syndrome (IBS) based on the Rome III or Rome IV diagnostic criteria. Pediatric populations (aged < 18 years), pregnant women, and lactating women were excluded to avoid confounding factors related to age or physiological status. • Comorbidity exclusion: Studies were excluded if participants had active confounding organic gastrointestinal diseases (e.g., inflammatory bowel disease, celiac disease, colorectal cancer), severe psychiatric disorders (e.g., major depressive disorder, schizophrenia), eating disorders (e.g., anorexia nervosa), or significant nutritional deficiencies. These comorbidities were considered likely to interfere with the implementation of dietary interventions or the accurate assessment of efficacy outcomes. 2.2.3 Interventions and comparators Eligible studies must have evaluated at least one of the four prespecified therapeutic dietary interventions (definitions were standardized for consistency across studies, as implemented in the included RCTs): Low FODMAP diet (LFD): Dietary pattern restricting fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) to < 10 g per day, consistent with current clinical guidelines for IBS management. Mediterranean diet (MD): Dietary pattern characterized by high intake of fruits, vegetables, whole grains, extra-virgin olive oil, fish, and legumes; with limited consumption of red meat and processed foods. This category included both pure MD and the Mediterranean-low FODMAP combination diet (MED-LFD). Traditional dietary advice (TDA): Specifically referring to NICE TDA (dietary advice based on the National Institute for Health and Care Excellence [NICE] guidelines for IBS management), a non-restrictive dietary guidance focusing on regular meal timing, portion control, and avoidance of common gastrointestinal irritants (e.g., high-fat foods, spicy foods, alcohol, caffeine); no strict restriction on specific nutrients was required. NICE TDA emphasizes evidence-based, patient-centered dietary recommendations tailored to IBS symptoms, consistent with the dietary advice applied in the included RCTs (Kasti AN 2025, Rej A 2022). Emerging therapeutic dietary interventions: Including the starch- and sucrose-reduced diet (SSRD) and gluten-free diet (GFD). Short-term FODMAP challenge studies were excluded, as they focus on mechanistic exploration rather than independent therapeutic interventions for IBS. Studies were eligible regardless of the type of comparator (e.g., other target dietary interventions, standard care, placebo diet), provided the above prespecified dietary interventions served as the core exposure and primary intervention of interest. 2.2.4 Distinction between therapeutic trials and mechanistic challenge studies In this review, we draw a clear conceptual and methodological distinction between two types of dietary studies relevant to IBS management, to ensure rigor in data synthesis and interpretation: (1) Therapeutic intervention trials: Studies that evaluate a predefined therapeutic dietary pattern (e.g., low FODMAP diet, Mediterranean diet, SSRD, GFD) as a long-term treatment strategy for IBS, with the intervention period typically lasting ≥ 4 weeks and primary outcomes focused on symptom improvement (e.g., IBS-SSS reduction ≥ 50 points), consistent with the therapeutic RCTs included in this review (Zhang Y 2021, Rej A 2022, Roth B 2024). (2) Mechanistic challenge (provocation) studies: Studies that administer high doses of specific dietary components (e.g., FODMAPs, gluten) for short periods (typically 1–7 days) to investigate whether these components trigger IBS symptoms, thereby testing causal hypotheses about the pathophysiological mechanisms of IBS. These studies do not aim to evaluate long-term dietary efficacy, consistent with the mechanistic studies included (Nordin E 2022/2023/2024). While both study types are included in this review, they serve fundamentally different purposes in the context of IBS dietary management. Therapeutic intervention trials constitute the primary evidence for evaluating the clinical efficacy of dietary interventions and are included in meta-analysis. Mechanistic challenge studies are used exclusively as supportive evidence to explain the pathophysiological rationale for dietary interventions and are not pooled or directly compared with therapeutic trials in the synthesis of efficacy outcomes. 2.2.5 Publication characteristics Language: Only full-text, peer-reviewed studies published in English were included (due to resource limitations in non-English language translation, validation, and quality assessment); Publication period: Studies published between January 2019 and December 2025 were included, consistent with the study’s focus on recent evidence to ensure clinical relevance; Duplicate publications: For overlapping patient data reported in multiple articles from the same research team, only the most comprehensive full-text version was retained after careful confirmation to avoid duplicate data inclusion. 2.2.6 Information sources and search strategy We systematically searched three major electronic databases: PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), covering the period from January 2019 to December 2025. The search strategy was developed based on the PICO framework, incorporating key terms related to irritable bowel syndrome (IBS) and each prespecified dietary intervention (LFD, MD, TDA, SSRD, GFD); the full search strategy for each database is available in the Supplementary Material. Additionally, reference lists of all included studies and relevant high-quality systematic reviews/meta-analyses were hand-searched to identify potential eligible studies. 2.3 Data extraction Two independent researchers systematically extracted data from all included peer-reviewed studies using a pre-designed and piloted data extraction form. The extracted items were structured to comprehensively cover core study characteristics and outcomes, consistent with the study’s research questions and eligible criteria, including: (1) Basic study information (first author, publication year, country, study design, funding source); (2) Participant characteristics (sample size [randomized, completed, and analyzed], age [mean ± standard deviation or median interquartile range], gender distribution, IBS subtype [IBS-C/D/M/U], diagnostic criteria [Rome III/IV], baseline symptom severity); (3) Intervention and comparator details (specific dietary definitions, implementation duration, intervention intensity, adherence monitoring measures, control measures, and any co-interventions); (4) Follow-up information (follow-up duration, assessment time points, and reasons for loss to follow-up); (5) Outcome data (efficacy: global symptom response rate, IBS-SSS score changes from baseline, subtype-specific symptom response; acceptability: adherence rate, implementation difficulty, patient preference, dropout rate; safety: incidence, type, and severity of adverse events, nutritional status indicators), consistent with the prespecified outcomes in Section 2.4 ; (6) Methodological details (randomization method, allocation concealment, blinding status of participants, personnel, and outcome assessors, and measures to minimize bias). To ensure data accuracy and reliability, a rigorous quality control process was implemented: • After initial independent extraction, the two researchers cross-validated all extracted data against the original study manuscripts and supplementary materials (if available); • Any discrepancies or ambiguities identified during cross-validation were resolved through group discussion. If consensus could not be reached, a third independent researcher arbitrated by re-examining the full text of the relevant study and documenting the resolution process. The final extracted data were compiled into a standardized spreadsheet for descriptive synthesis and meta-analysis. 2.4 Outcome measures 2.4.1 Efficacy outcomes The primary efficacy outcome was clinical response rate, defined as a reduction of ≥ 50 points in the Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) from baseline or patient-reported adequate relief of core IBS symptoms (abdominal pain, bloating, altered bowel habits) for ≥ 7 consecutive days (Roth et al. [2024], Wang et al. [2021]). Secondary efficacy outcomes included absolute changes in total IBS-SSS score, ≥ 30% reduction in abdominal pain and bloating severity (assessed by 100-mm visual analog scale [VAS]), improvements in stool consistency (Bristol Stool Form Scale) and frequency, as well as changes in the 34-item IBS-specific quality of life (IBS-QoL) score. 2.4.2 Acceptability outcomes Indicators were defined in alignment with included RCTs and systematic reviews (Haghbin et al. [2024]; Rej et al. [2022]): adherence rate (proportion of patients completing the intervention as required), dropout rate (proportion of patients withdrawing during intervention/follow-up), implementation difficulty (patient-reported 5-point Likert scale: 1 = extremely easy to 5 = extremely difficult; scores ≥ 4 = high difficulty), and monthly direct dietary cost (converted to US dollars for consistency, excluding indirect costs). 2.4.3 Safety outcomes Included the incidence, type, and severity of adverse events (AEs: mild=spontaneous resolution, moderate=symptomatic intervention required, severe=intervention discontinuation) and serious adverse events (SAEs: events leading to death, hospitalization, life-threatening conditions, or persistent disability) (Algera et al. [2022]; Roth et al. [2024]). 2.5 Risk of bias assessment The methodological quality of included randomized controlled trials (RCTs) was evaluated using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool. Key bias domains assessed included random sequence generation, allocation concealment, blinding of participants/personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other potential biases. For crossover RCTs (a major design among included studies), the RoB 2.0 crossover-specific module was applied, with additional evaluation of two critical domains: adequacy of washout period (≥ 1 week was considered adequate) and presence of carryover effect (assessed by comparing symptom scores between first and second intervention periods). The overall risk of bias for each study was defined a priori: "low risk" if no domains were rated high risk and unclear risk domains ≤ 2; otherwise "high risk" or "some concerns". Bias assessments were conducted independently by two researchers, with discrepancies resolved through re-examining original studies or arbitration by a third researcher. Detailed risk of bias ratings for each study are presented in Table 3 , and a visual summary of overall bias distribution is shown in Fig. 2 . 2.6 Data synthesis and statistical analysis Data synthesis was conducted in accordance with the PRISMA-NMA (Network Meta-Analyses) statement. Instead of traditional pairwise comparisons, a frequentist network meta-analysis (NMA) was performed to simultaneously compare multiple dietary interventions (LFD, MD, MED-LFD, TDA, SSRD, GFD, and Habitual/Control) using the netmeta package (version 2.8-1) in R software (version 4.3.0). For the primary efficacy outcome (clinical response rate), risk ratios (RR) with 95% confidence intervals (CIs) were calculated. A random-effects model was employed to account for anticipated clinical and methodological heterogeneity. Network geometry was visualized using network plots, where node size reflects the sample size of each intervention and edge thickness represents the number of direct comparisons. To rank the relative efficacy of all dietary interventions, we calculated the P-score (a frequentist analog to the Surface Under the Cumulative Ranking curve [SUCRA]), which ranges from 0 to 1; a higher P-score indicates a higher probability of being the most effective treatment. Global heterogeneity and inconsistency were assessed using Cochran’s Q statistic. To evaluate local inconsistency between direct and indirect evidence, the node-splitting method was applied, with P < 0.05 indicating significant inconsistency. Sensitivity analyses were conducted by strictly applying intention-to-treat (ITT) data to ensure the robustness of the network estimates. Publication bias was visually evaluated using a comparison-adjusted funnel plot. 3. Results 3.1 Study Selection and Flow of Studies The flow of study selection is summarized in the PRISMA 2020 flow diagram (Figure 1). A total of 3304 records were initially identified through database searches (PubMed, Embase, Cochrane Library, and Web of Science). After removing duplicate records, 2825 unique records remained for title and abstract screening. Of these, 2779 records were excluded (irrelevant topic, not IBS population or not a dietary intervention), leaving 36 full-text articles for eligibility assessment. During full-text review, 36 articles were excluded for the following reasons: n = 8: not an RCT; n = 7: wrong patient population; n = 8: no relevant clinical response outcome; n = 13: non-target dietary intervention]. Finally, 10 RCTs were included in the systematic review and meta-analysis, consistent with the risk of bias assessment and quantitative synthesis described below. 3.2 Study Characteristics and Descriptive Therapeutic Efficacy Results A total of 10 independent randomized controlled trials (RCTs) focusing on therapeutic dietary interventions, published from 2019 to 2025, were included in this systematic review, involving 939 adult patients diagnosed with irritable bowel syndrome (IBS). These studies were conducted across four countries: China, Sweden, the United States of America, and Greece. Regarding IBS subtypes, most studies enrolled patients with diarrhea-predominant IBS (IBS-D), mixed IBS (IBS-M), and non-constipated IBS, with a small proportion of patients with constipation-predominant IBS (IBS-C) and unclassified IBS (IBS-U). Intervention durations ranged from 1 week (for crossover trial periods) to 6 months, with the majority of therapeutic trials having a duration of ≥4 weeks. All included studies evaluated at least one of the four prespecified dietary intervention categories: low FODMAP diet (LFD), Mediterranean diet (MD, including the combined Mediterranean-low FODMAP diet [MED-LFD]), traditional dietary advice (TDA), and emerging dietary interventions (starch-sucrose reduced diet [SSRD] and gluten-free diet [GFD]). Comparators in the included RCTs included other dietary interventions, habitual diet, and placebo, with detailed information provided in Table 1 . The raw dichotomous data (clinical response rate) used for the meta-analysis of the included studies are presented in Supplementary Material eTable 1. 3.2.1 Therapeutic intervention trials 3.2.1.1 Low FODMAP diet (LFD) In therapeutic intervention trials, the efficacy of the low FODMAP diet (LFD) varied depending on study design, response definition, and intervention intensity. In the therapeutic intervention trials, intention-to-treat (ITT) analysis revealed consistent short-term efficacy for LFD. Zhang Y (2021) reported a responder rate of 55.6% (30/54) [1], while Roth B (2024) demonstrated a 4-week ITT response rate of 78.2% (61/78) [11]. Singh P (2025) reported an 81.8% (9/11) response rate in a pilot study, achieving significant symptom reduction [6]. Even in the short-term crossover trial by Algera JP (2022), 34.5% (10/29) of patients met the response criteria within one week of strict FODMAP restriction [5]. These findings confirm LFD's efficacy across a spectrum of 34.5% to 81.8%. Additionally, 22% (6/29) of patients experienced symptom worsening (≥50-point IBS-SSS increase) during the moderate FODMAP period, indicating FODMAP sensitivity [5]. These findings confirm the short-term efficacy of LFD but highlight a wide response range (34%-78%), underscoring that responder definitions and the degree of FODMAP restriction critically impact efficacy estimates. 3.2.1.2 Mediterranean diet (MD) Three randomized controlled trials (RCTs) investigated the efficacy of Mediterranean-style diets, including pure Mediterranean diet (MD) and the combined Mediterranean-low FODMAP diet (MED-LFD). Bamidele JO (2025) conducted a high-quality randomized non-inferiority trial (n=139) comparing MD with TDA over 6 weeks. In the modified intention-to-treat (mITT) analysis, MD demonstrated not only non-inferiority but statistical superiority to TDA, with a clinical response rate (IBS-SSS reduction ≥50 points) of 61.8% (42/68) compared to 42.3% (30/71) in the TDA group (risk difference 20%, 95% CI: 4%–36%; P=0.017) [17]. Furthermore, the MD group showed a significantly greater reduction in mean IBS-SSS scores than the TDA group (−101.2 vs. −64.5; P=0.034) [17]. These findings are supported by a pilot feasibility study by Singh P (2025) (n=22), which reported that 72.7% (8/11) of the MD group met the FDA responder definition for abdominal pain intensity (API) relief (≥30% reduction). However, in terms of global IBS-SSS response (≥50-point reduction), the MD group in this pilot study showed a lower response rate compared to the strict LFD group (45.5% vs. 81.8%), with the LFD group achieving a significantly greater absolute reduction in IBS-SSS (−105.5 vs. −60, P=0.02) [6]. Kasti AN (2025) evaluated the MED-LFD hybrid approach in a parallel RCT (n=108). The MED-LFD group demonstrated excellent and sustained efficacy in the ITT analysis: the clinical response rate (IBS-SSS reduction ≥50 points) was 81.5% (44/54) at the first follow-up and remained high at 70.4% (38/54) at the 6-month follow-up [7]. These rates were significantly superior to the NICE-based TDA group at both time points (57.4% and 42.6%, respectively; P=0.007, P=0.004). Crucially, the intervention was identified as the strongest independent predictor of clinical response (OR 6.66 at first follow-up; OR 4.85 at 6 months). The MED-LFD also significantly improved IBS-related quality of life (IBS-QoL) and psychological markers, including anxiety and depression scores (P<0.001 for all) [7]. 3.2.1.3 Traditional dietary advice (TDA) Traditional dietary advice demonstrated moderate but stable clinical efficacy across included studies, with clinical response rates ranging from 42% (95% CI: 31.8%–52.7%) to 48.1% (95% CI: 37.8%–58.5%) [1,9]. Rej A (2022) found no statistically significant differences in response rates among TDA (42%), LFD (55%), and GFD (58%) (overall P=0.43), indicating that TDA can provide symptomatic relief but may not be superior to more structured dietary interventions [9]. Kasti AN (2025) further confirmed that TDA was less effective than MED-LFD, with a significantly lower response rate at both follow-up time points [7]. 3.2.1.4 Emerging diets (SSRD and GFD) Starch-sucrose reduced diet (SSRD) SSRD demonstrated robust non-inferiority to LFD and clear superiority over habitual diets. Roth B (2024) reported a responders rate of 79.2% (61/77) for SSRD, confirming its non-inferiority to LFD (78.2%, 61/78) [11]. In parallel RCTs, Nilholm C (2022) and Nilholm C (2019) reported consistent ITT response rates of 73.1% (57/78) and 71.2% (57/80), respectively, which were significantly superior to habitual diet controls (24.0% and 28.0%; P<0.001) [10]. Moreover, 28.2% of patients in the SSRD group no longer fulfilled the Rome IV criteria for FGID/IBS at 4 weeks, compared to 0% in the control group (P<0.001), indicating that SSRD can induce clinical remission in a subset of patients [10]. In a pre-specified exploratory analysis of patients who tried both SSRD and LFD (n=34), 64.7% (22/34) preferred SSRD, citing ease of adherence and better tolerability as the primary reasons. At the 6-month follow-up, 52.8% of patients in the SSRD group continued to follow a modified version of the diet, compared to 36.7% in the LFD group (P=0.005), suggesting better long-term acceptability of SSRD [11]. Gluten-free diet (GFD) The efficacy of GFD showed marked heterogeneity across studies. Rej A (2022) reported a 58% responder rate (≥50-point IBS-SSS reduction) in the GFD group, with no significant difference from LFD (55%) or TDA (42%) (P=0.43) [9]. However, using a stricter "true responder" definition (symptom improvement only during the gluten-free period, with no improvement during the washout period), Algera JP (2022) found that only 30% (6/20) of patients were true responders to GFD [3]. Mechanistic studies by Nordin E and colleagues consistently demonstrated that gluten challenges did not induce significant symptom worsening in IBS patients, while high-FODMAP challenges did [2,4,5]. This mechanistic insight elegantly suggests that the symptom improvement observed in some GFD therapeutic trials (such as Rej 2022) is highly likely confounded by the concurrent reduction of specific FODMAPs—particularly fructans present in wheat—rather than a specific therapeutic effect of gluten removal per se. Therefore, GFD cannot be recommended as a first- or second-line intervention for the general IBS population. Its benefit is likely confined to a distinct subset of patients, such as those with suspected non-celiac gluten sensitivity, and requires further large-scale studies to confirm its efficacy and identify predictive factors. Therefore, while SSRD emerges as a highly promising, sustainable alternative to LFD for the general IBS population, GFD should be deprioritized and reserved strictly for patients with suspected non-celiac gluten sensitivity (NCGS). The key efficacy outcomes, mechanistic evidence, and interpretive summary for each dietary intervention are presented in Table 2. First author, Year Country Study design Sample size (Intervention/Control) Intervention Comparator IBS subtype Follow-up Main outcome Zhang Y, 2021 China Randomized, parallel-group, controlled trial 108 randomized LFD : 54 (51 completed) TDA : 54 (49 completed) Low FODMAP diet (LFD) Traditional dietary advice (TDA) IBS-D (diarrhea-predominant) 3 weeks (intervention period) IBS-SSS ≥50 reduction Algera JP, 2022 Sweden Double-blind, randomized, placebo-controlled, crossover trial 29 completed at least one intervention period Low FODMAP period : 28 completed Moderate FODMAP period : 27 completed Low FODMAP diet (4 g/day) Moderate FODMAP diet (23 g/day) IBS-C (21%), IBS-D (38%), IBS-M (31%), IBS-U (3%) 1 week per intervention period IBS-SSS ≥50 reduction Singh P, 2025 USA Pilot, feasibility, randomized controlled trial (feeding study) 26 randomized; 22 included in mITT analysis; 20 completed (10 per group) MD : 15 randomized, 10 completed LFD : 11 randomized, 10 completed Mediterranean diet (MD) – provided meals for 4 weeks Low FODMAP diet (LFD) – provided meals for 4 weeks IBS-D (diarrhea-predominant) and IBS-M (mixed bowel pattern) 4 weeks (intervention period) Abdominal pain ≥30% reduction Kasti AN, 2025 Greece Randomized, parallel-group, controlled trial 108 randomized (54 per group) MED-LFD : 54 (52 completed first follow-up; 48 completed second follow-up) NICE : 54 (51 completed first follow-up; 44 completed second follow-up) Mediterranean low-FODMAP diet (MED-LFD) – restrictive phase (2–6 weeks), reintroduction phase (6–8 weeks), then personalized long-term diet NICE dietary guidelines for IBS (4-week plan with monitoring at 6 months) Non-constipation IBS (IBS-D and IBS-M) First follow-up: after restrictive phase (MED-LFD) or 4 weeks (NICE) Second follow-up: 6 months after baseline IBS-SSS ≥50 reduction Rej A, 2022 United Kingdom Randomized, parallel-group, controlled trial (three arms) 99 completed (33 per arm) TDA : 33 LFD : 33 GFD : 33 • Traditional dietary advice (TDA) – based on NICE guidelines • Low FODMAP diet (LFD) – 4-week elimination phase • Gluten-free diet (GFD) – allowing minute cross-contamination Three diets compared head-to-head (no placebo) Non-constipated IBS (IBS-D and IBS-M) 4 weeks (intervention period) IBS-SSS ≥50 reduction Algera JP, 2022 Sweden Double-blind, randomized, placebo-controlled, crossover trial 20 IBS patients; 18 healthy controls completed Gluten-free period : 20 IBS patients Gluten-containing period : 20 IBS patients Gluten-free diet + gluten powder (14 g/day) for 2 weeks Gluten-free diet + rice flour powder (placebo) for 2 weeks IBS-C (25%), IBS-D (40%), IBS-M (30%), IBS-U (5%) 2 weeks per intervention period IBS-SSS ≥50 reduction Nilholm C, 2022 Sweden Randomized, parallel-group, controlled trial 103 included in analysis Intervention (SSRD) : 78 Control (habitual diet) : 25 Starch- and sucrose-reduced diet (SSRD) for 4 weeks – focusing on reduced intake of confectionary, soda, processed foods; increased intake of meats, fish, dairy, eggs, nuts, seeds, selected fruits/vegetables low in starch/sucrose Habitual diet (no dietary advice) IBS-D (25.2%), IBS-M (35.9%), IBS-C (18.4%), Unspecified IBS (2.9%), Non-IBS FGID (15.6%) 4 weeks (intervention period) IBS-SSS ≥50 reduction Roth B, 2024 Sweden Randomized, open-label, parallel-group, non-inferiority trial 155 randomized SSRD : 77 (72 completed 4 weeks; 53 completed 6 months) Low FODMAP : 78 (72 completed 4 weeks; 49 completed 6 months) Starch- and sucrose-reduced diet (SSRD) – 4-week intervention focusing on reduced intake of sucrose, starch, added sugar; increased intake of protein, fat, non-starchy vegetables, fruits, dairy, meat, fish Low FODMAP diet – 4-week elimination phase followed by reintroduction and personalization IBS-C (16.8%), IBS-D (28.4%), IBS-M (34.8%), IBS-U (4.5%), Unspecific functional bowel disorder (15.5%) 2 weeks, 4 weeks (end of intervention), 6 months (without mandatory dietary restrictions) IBS-SSS ≥50 reduction Nilholm C, 2019 Sweden Randomized, open-label, parallel-group controlled trial Intervention: 80 Control: 25 Starch- and sucrose-reduced diet (SSRD) – 4 weeks Habitual diet (no dietary advice) Mixed (IBS-C, IBS-D, IBS-M, FGID) 4 weeks IBS-SSS ≥50 reduction Bamidele JO, 2025 United Kingdom Randomized, open-label, parallel-group, non-inferiority trial MD : 68 (modified ITT) TDA : 71 (modified ITT) Mediterranean diet (MD) – 6 weeks Traditional dietary advice (TDA) – based on British Dietetic Association guidelines Mixed (48% mixed, 31% diarrhea, 21% constipation) 6 weeks IBS-SSS ≥50 reduction Table 1: Baseline characteristics of the 10 included randomized controlled trials Diet type Efficacy findings from therapeutic trials Efficacy findings from mechanistic challenge studies (supportive evidence) Key efficacy interpretation Low FODMAP (LFD) Zhang 2021 [1] : LFD responder rate 55.6%; Roth 2024 [11] : LFD 4-week responder rate 78.2%; Algera 2022 [5] : 34% responder rate, with 22% FODMAP-sensitive. Nordin 2022 [2] : High-FODMAP challenge significantly increased IBS-SSS vs. placebo (P=0.00056). High short-term efficacy; adequate restriction is necessary for therapeutic benefit; mechanistic studies confirm FODMAPs trigger symptoms. Mediterranean ( MD / MED-LFD ) Kasti 2025 [7] (MED-LFD): Responder rate 81.5% at first follow-up, 70.4% at 6 months. Singh 2025 [6] (Pure MD): Abdominal pain relief rate 72.7% Not applicable MED-LFD demonstrates excellent long-term efficacy and sustained symptom control; pure MD shows promise. Traditional dietary advice (TDA) Zhang 2021 [1] : TDA responder rate 48.1%; Rej 2022 [8] : TDA responder rate 42%; Kasti 2025 [7] : TDA responder rate 57.4%. Not applicable Moderate but stable efficacy; most accessible, highly acceptable, and cost-effective option. SSRD Nilholm 2022 [10] : SSRD responder rate 73.1%. Roth 2024 [11] : SSRD responder rate 79.2%; 64.7% preferred SSRD over LFD; Long-term adherence at 6 months: SSRD 52.8% vs. LFD 36.7%. Not applicable Non-inferior efficacy to LFD with higher patient preference and better long-term adherence. Emerging: GFD Rej 2022 [8] : GFD responder rate 58%. Algera 2022 [9] : True responder rate (response only to GFD): 30%. Nordin 2022/2023/2024 [2,4,5] : Gluten challenge showed no significant difference from placebo at group level. High efficacy heterogeneity; benefit likely limited to NCGS subset; efficacy in unselected IBS likely confounded by incidental FODMAP reduction. Table 2. Efficacy outcomes of dietary interventions for patients with irritable bowel syndrome (IBS). Abbreviations: LFD = low FODMAP diet; MD = Mediterranean diet; MED-LFD = Mediterranean low FODMAP diet; TDA = traditional dietary advice; SSRD = starch-sucrose-reduced diet; GFD = gluten-free diet; IBS-SSS = Irritable Bowel Syndrome Symptom Severity Score; ITT = intention-to-treat; CI = confidence interval; RCT = randomized controlled trial. Notes: Clinical response rate is defined as the percentage of patients achieving a reduction of ≥50 points in the IBS-SSS, unless otherwise specified. 3.3 Risk of Bias Assessment Risk of bias for all included randomized controlled trials (RCTs) was assessed using the Cochrane RoB 2.0 tool for randomized trials, which evaluates six core domains: (1) random sequence generation (2) allocation concealment, (3) blinding of participants and personnel (4) blinding of outcome assessors (5) incomplete outcome data (6) selective reporting. An additional domain of "other bias" (e.g., baseline imbalance, small sample size, conflict of interest) was also considered. Detailed domain-specific ratings for each study are summarized in Table 3, and a visual summary of overall risk of bias is presented in Figure 2 3.3.1 Domain-specific Risk of Bias Random sequence generation: 10 studies were rated as low risk (e.g., computer-generated randomization, random number tables), while 0 studies were rated as unclear risk due to insufficient reporting of sequence generation methods. No studies were rated as high risk in this domain. Allocation concealment: 4 studies were rated as low risk (e.g., central randomization, sealed opaque envelopes), and 6 studies were rated as unclear risk (no description of concealment methods). No high-risk studies were identified here. Blinding of participants and personnel: Due to the nature of dietary interventions (impossible to blind participants/staff to assigned diets), all studies were rated as high risk of performance bias. 0 studies were rated as unclear risk (no mention of blinding or mitigation strategies). This was the primary domain with high risk of bias across all included trials. Blinding of outcome assessors: 8 studies were rated as low risk (blinded assessors for subjective outcomes like IBS-SSS), while 2 studies were unclear risk (no reporting of assessor blinding). No high-risk studies were found here. Incomplete outcome data: 10 studies were rated as low risk (low loss-to-follow-up <10%, intention-to-treat analysis), and 0 studies were unclear risk (no reporting of missing data handling). No high-risk studies were identified. Selective reporting: 10 studies were rated as low risk (registered in clinical trial databases, all pre-specified outcomes reported), while 0 studies were unclear risk (no trial registration or incomplete outcome reporting). No high-risk studies were found. Other bias: 8 studies were rated as low risk (no baseline imbalance, adequate sample size), while 2 studies were unclear risk (small sample size <50 per arm, potential baseline imbalance). No high-risk studies were identified. 3.3.2 Overall Risk of Bias Overall, the included RCTs were rated as having moderate overall risk of bias. The main limitation was high risk of performance bias (due to unavoidable lack of blinding in dietary interventions), while all other domains were predominantly low or unclear risk. No study was rated as high risk in more than one domain, suggesting the meta-analytic results are generally reliable, though subjective symptom outcomes may be slightly influenced by performance bias. Study Design Type Study (First author, Year) RS AC BPP BOA IOD SR OB Overall risk of bias Parallel RCT Zhang Y, 2021 Low Unclear High Low Low Low Low Moderate Parallel RCT Rej A, 2022 Low Unclear High Low Low Low Unclear Moderate Crossover RCT Algera JP, 2022 (GFD) Low Unclear High Unclear Low Low Low Moderate Crossover RCT Algera JP, 2022 (Low FODMAP) Low Unclear High Low Low Low Low Moderate Parallel RCT Nilholm C, 2022 Low Low High Low Low Low Low Moderate Non-inferior RCT Roth B, 2024 Low Low High Low Low Low Low Moderate Parallel RCT Kasti AN 2025 Low Unclear High Low Low Low Low Moderate Pilot RCT Singh P, 2025 Low Unclear High Unclear Low Low Unclear Moderate Parallel RCT Bamidele JO, 2025 Low Low High Low Low Low Low Moderate Parallel RCT Nilholm C, 2019 Low Low High Low Low Low Low Moderate Table 3. Risk of bias assessment of the 10 included randomized controlled trials using the Cochrane Risk of Bias 2.0 tool. Abbreviations: RS, random sequence generation; AC, allocation concealment; BPP, blinding of participants and personnel; BOA, blinding of outcome assessment; IOD, incomplete outcome data; SR, selective reporting; OB, other bias; Low, low risk of bias; Unclear, unclear risk of bias. Notes: Blinding of participants and personnel was rated as high risk for all studies due to the inherent impossibility of blinding dietary interventions in real-world feeding or guidance trials. Therefore, the "Overall risk of bias" for all included trials is classified as "Moderate" (Some concerns). 3.4 Network Meta-analysis of Clinical Efficacy 3.4.1 Network Geometry A connected network was successfully constructed comprising 7 distinct nodes: LFD, MD, MED-LFD, TDA, SSRD, GFD, and Habitual/Control. The network incorporated 10 RCTs encompassing 939 participants. LFD and TDA served as the primary hub nodes, forming a robust closed-loop network geometry. 3.4.2 Relative Efficacy of Dietary Interventions (League Table) The league table of the network meta-analysis provided pairwise comparisons across all interventions. Compared with the Habitual/Control diet, all structured interventions demonstrated statistically significant superiority in achieving clinical response. Converting the network estimates to standard Risk Ratios (RR, Treatment vs. Control), MED-LFD exhibited the most robust treatment effect (RR = 2.37, 95% CI: 1.38–4.07), followed by SSRD (RR = 2.25, 95% CI: 1.52–3.34), MD (RR = 2.25, 95% CI: 1.35–3.75), LFD (RR = 2.17, 95% CI: 1.45–3.25), and GFD (RR = 2.10, 95% CI: 1.26–3.50). TDA showed relatively lower efficacy (RR = 1.67, 95% CI: 1.04–2.68). Control GFD LFD MD MED-LFD SSRD TDA Control Control 0.83 (0.30, 2.29) 0.60 (0.25, 1.43) . . 0.36 (0.22, 0.58) . GFD 0.48 (0.29, 0.79) GFD 1.06 (0.69, 1.62) . . . 1.36 (0.83, 2.22) LFD 0.46 (0.31, 0.69) 0.97 (0.67, 1.41) LFD 1.13 (0.71, 1.78) . 0.99 (0.84, 1.16) 1.20 (0.89, 1.61) MD 0.44 (0.27, 0.74) 0.94 (0.59, 1.48) 0.96 (0.70, 1.33) MD . . 1.46 (1.05, 2.03) MED-LFD 0.42 (0.25, 0.73) 0.89 (0.55, 1.43) 0.92 (0.63, 1.33) 0.95 (0.65, 1.40) MED-LFD . 1.42 (1.09, 1.85) SSRD 0.44 (0.30, 0.66) 0.93 (0.63, 1.39) 0.96 (0.82, 1.13) 1.00 (0.70, 1.43) 1.05 (0.70, 1.57) SSRD . TDA 0.60 (0.37, 0.96) 1.26 (0.85, 1.88) 1.30 (1.00, 1.69) 1.35 (1.02, 1.79) 1.42 (1.09, 1.85) 1.35 (0.99, 1.83) TDA Table4. League Table Data are presented as Risk Ratios (RRs) with 95% Confidence Intervals. The lower-left triangle indicates pooled NMA estimates (random-effects model); the upper-right triangle indicates direct pairwise evidence. An RR > 1 favors the intervention in the row compared to the column. MED-LFD ranked first with a P-score of 0.76. 3.4.3 Treatment Ranking (P-scores) According to the P-score ranking matrix, which evaluates the probability of each diet being the best intervention for achieving clinical response, the hierarchy of efficacy was established as follows: MED-LFD (P-score = 0.7592) SSRD (P-score = 0.6970) MD (P-score = 0.6795) LFD (P-score = 0.6001) GFD (P-score = 0.5634) TDA (P-score = 0.1973) Habitual/Control (P-score = 0.0036) 3.4.4 Heterogeneity and Inconsistency Analysis The robustness of the network model was highly satisfactory. The global inconsistency test showed no significant disparity between the direct and indirect network designs. Crucially, the node-splitting method confirmed local consistency across all closed loops, with all P-values well above the significance threshold (ranging from 0.137 to 0.623), indicating robust agreement between direct and indirect evidence. Furthermore, the comparison-adjusted funnel plot demonstrated a highly symmetric distribution, suggesting an absence of significant publication bias or small-study effects. 3.5 Acceptability and Safety 3.5.1 Acceptability Traditional dietary advice (TDA) demonstrated superior acceptability across patient-reported measures. Rej A (2022) reported that TDA was perceived as significantly cheaper (49% of TDA patients reported increased cost vs 82% for GFD and LFD; P<0.01), less time-consuming for grocery shopping (39% of TDA patients reported extra time vs 79% for LFD and 70% for GFD; P<0.01), and easier to follow when eating out (52% of TDA patients reported difficulty vs 67% for LFD and GFD; P=0.03) [9]. TDA was also easier to incorporate into daily life than LFD (55% of TDA patients reported easy incorporation vs 33% for LFD; P=0.02) [8]. The Mediterranean diet (including combined MED-LFD) showed favorable acceptability. Kasti AN (2025) reported a 75% adherence rate ("most of the time" or "every day") and 96.3% follow-up completion rate at first follow-up [7]. A pure Mediterranean diet pilot study reported 93.8% compliance based on 3-day food diaries [6]. LFD showed moderate acceptability. Roth B (2024) reported good short-term adherence (78.2% response rate at 4 weeks), but only 36.7% of patients continued a personalized LFD at 6-month follow-up [11]. Patients reported challenges with strict FODMAP calculation and increased shopping time [9,11]. A feeding trial with provided meals reported 94% compliance, reflecting an idealized rather than real-world setting [8]. SSRD demonstrated higher patient preference and long-term adherence compared with LFD. Among patients who tested both diets, 64.7% (22/34) preferred SSRD, citing ease of adherence (16 patients) or combined ease and efficacy (7 patients) [11]. At 6-month follow-up, 52.8% of SSRD patients continued a modified diet vs 36.7% of LFD patients (P=0.005), supporting better long-term acceptability [11]. Dropout rates across all studies ranged from 3.7% to 23.1%, with the lowest rates in TDA and MED-LFD groups (3.7%–9.5%) [6,7,8] and higher rates in LFD and GFD groups (11.1%–23.1%) [5,8,11]. 3.5.2 Safety All four dietary interventions were safe and well-tolerated, with no serious adverse events (SAEs) reported in any included study [1-11]. Mild adverse events were predominantly transient, self-limiting gastrointestinal symptoms related to dietary adaptation. LFD: Transient bloating was reported during initial adaptation [8]. One case of constipation led to study withdrawal in the strict LFD subgroup (4 g/day) [6]; all other mild events resolved spontaneously. Mediterranean diet (including MED-LFD): Occasional mild bloating was observed, with 8 non-specific adverse events (headache, fatigue, mild abdominal worsening) equally distributed across treatment arms [7]. No patients withdrew due to adverse events in the MED-LFD group [7]; one patient in the pure Mediterranean diet pilot withdrew due to worsening abdominal pain [6]. TDA: The lowest incidence of mild adverse events was reported, with minimal transient gastrointestinal symptoms that resolved rapidly [6,9]. SSRD: No adverse events related to dietary restriction were reported during long-term follow-up [11]; any initial transient digestive symptoms were mild and self-limiting [6]. With the exception of two withdrawals in the Singh P (2025) pilot study (one LFD-related constipation, one Mediterranean diet-related abdominal pain), no patients withdrew from studies due to adverse events [6]. A concise comparison of acceptability, adherence, dropout rates, and safety profiles of the four main dietary interventions is provided in Table 4. Diet type Acceptability Adherence Dropout rate Safety Low FODMAP Moderate 78%–95% 19%–23.1% Bloating reported (occasional); one case of constipation leading to withdrawal [8]; onset during adaptation period (1-2 weeks), spontaneous resolution Mediterranean High 75% (Kasti 2025) [7] 3.7%–5.8% [7,8] Eight AEs reported (headache, fatigue, abdominal symptoms) [7]; one withdrawal due to abdominal pain (pure MD) [8]; all transient Traditional Highest >95% (inferred) 5.8%–9.5% [6,9] Minimal reports of transient gastrointestinal symptoms; rapid spontaneous resolution Emerging (SSRD) High >90% (inferred) <10% (short-term) [6,11] Occasional bloating reported; transient and self-limiting; no AEs during long-term follow-up [11] Table 4. Acceptability and safety outcomes of dietary interventions for patients with irritable bowel syndrome (IBS). Abbreviations: IBS = irritable bowel syndrome; SSRD = starch-sucrose-reduced diet; AEs = adverse events; MD = Mediterranean diet. Notes: Adherence and dropout rates are presented as ranges across included studies or single-study values where only one study reported the outcome. Acceptability ratings (Moderate/High/Highest) are based on subjective patient-reported outcomes from the included trials. All reported adverse events were mild and transient; no serious adverse events (SAEs) were documented in any study [1-11]. 4. Discussion 4.1 Key Findings The present systematic review and meta-analysis included 10 randomized controlled trials (RCTs) enrolling 939 adult patients with irritable bowel syndrome (IBS), comprehensively evaluating the efficacy, acceptability, and safety of four dietary interventions: the low FODMAP diet (LFD), Mediterranean diet (including pure MD and Mediterranean-low FODMAP hybrid diet [MED-LFD]), traditional dietary advice (TDA), and Emerging diet (SSRD, GFD). The core findings are summarized as follows: 1. Efficacy Outcomes and Hierarchy of Dietary Interventions A major contribution of this study is the establishment of a clear efficacy hierarchy among IBS dietary interventions through network meta-analysis (NMA), overcoming the limitations of previous traditional pairwise meta-analyses that often clumped distinct control diets into ambiguous categories. Our NMA definitively ranked the hybrid MED-LFD as the most effective intervention (P-score = 0.76). This indicates that combining the anti-inflammatory benefits of a Mediterranean pattern with the osmotic and fermentative reduction of LFD yields synergistic therapeutic effects, offering excellent and sustained symptom control. Notably, SSRD emerged as the second highest-ranking diet (P-score = 0.70), outperforming the classical LFD (P-score = 0.60). This robust statistical evidence confirms that targeting sucrase-isomaltase pathways through starch and sucrose reduction is a highly viable, non-inferior alternative to FODMAP restriction, particularly given its superior patient preference and long-term adherence reported in descriptive analyses. While TDA demonstrated statistical superiority over habitual diets, it consistently ranked near the bottom among structured therapies (P-score = 0.20), suggesting that unstructured advice, despite its ease of implementation, should ideally serve as a baseline or adjunctive strategy rather than a definitive standalone treatment for moderate-to-severe IBS. 2. Acceptability and Safety All interventions were generally safe, with no serious adverse events reported; mild adverse events (e.g., transient bloating, flatulence) were self-limiting. TDA had the highest acceptability, attributed to lower financial cost and reduced time burden for patients, alongside the lowest dropout rates (3.7%–9.5%), comparable to MED-LFD. SSRD demonstrated better long-term adherence and patient preference compared with LFD, likely due to less restrictive dietary rules, while LFD showed acceptable short-term adherence but higher dropout rates in long-term follow-up. 4.2 Mechanistic Rationale and Interpretation of Heterogeneity Mechanistic challenge studies provide the critical pathophysiological rationale for dietary interventions and help interpret the heterogeneity observed in therapeutic trials. A series of double-blind, placebo-controlled crossover studies by Nordin et al. confirmed that FODMAPs, but not gluten, are specific triggers of IBS symptoms at the group level [2,4,5]. In their 2022 study, high-dose FODMAP intervention (50 g/day) significantly exacerbated IBS-SSS scores compared with placebo (mean 240 vs. 198; P=0.00056), while gluten challenge (17.3 g/day) showed no significant difference from placebo [2]. These findings validate the therapeutic rationale for FODMAP restriction, explaining why LFD yields consistent clinical efficacy across diverse study settings (low heterogeneity, I²=0%). Conversely, the high heterogeneity observed in GFD trials and the variable efficacy of GFD in clinical trials can be mechanistically explained by these data. The lack of a consistent symptomatic response to isolated gluten challenge suggests that symptom improvement in some GFD trials may be attributable to the concurrent reduction of FODMAPs (e.g., fructans in wheat) rather than gluten removal per se [3,9]. Therefore, GFD is not universally effective for the general IBS population; its benefit is likely confined to a small subset of patients with underlying gluten sensitivity, for whom reliable predictors remain to be established. 4.3 Comparison with Previous Studies Our findings align with prior systematic reviews demonstrating that LFD is a consistent, well-tolerated dietary intervention for IBS, but not superior to other evidence-based dietary strategies. The inferior efficacy of TDA observed in our analysis is consistent with clinical consensus that unstructured, general dietary advice yields weaker outcomes compared with structured, mechanism-targeted diets (e.g., LFD, SSRD). Notably, our study extends previous findings by evaluating the crucial balance between short-term efficacy and long-term nutritional safety. Previous systematic reviews, such as Wang et al. (2021) [12], have highlighted that while traditional LFD provides rapid symptom relief, its long-term strict implementation raises concerns regarding nutritional inadequacy and significant reductions in beneficial gut microbiota (e.g., Bifidobacteria ). In contrast, our network analysis underscores the superiority of the hybrid MED-LFD approach, aligning with the recent groundbreaking findings by Kasti et al. (2025) [7]. By embedding low-FODMAP principles within a Mediterranean dietary pattern, the MED-LFD not only mitigates the nutritional limitations of traditional LFD but also harnesses the anti-inflammatory and microbiome-modulating properties of Mediterranean polyphenols and omega-3 fatty acids. This synergy likely explains its top-ranking efficacy and profound improvements in IBS-related quality of life (IBS-QoL) and psychological well-being. For emerging interventions, the non-inferiority of SSRD to LFD supports its potential as a more sustainable alternative, whereas the high heterogeneity in GFD trials suggests its benefits are likely confined to non-celiac gluten sensitivity subgroups rather than the general IBS population. 4.4 Clinical Implications: A Stepped Dietary Therapy Framework Based on our network meta-analysis, combined with acceptability and mechanistic evidence, we propose a stepped, personalized dietary therapy framework for IBS management: First-line therapy (Low burden & High acceptability): TDA. As highlighted by Rej et al. [8], while highly structured diets like LFD and GFD show robust clinical efficacy, TDA significantly outperforms them in patient acceptability, cost-effectiveness, and ease of real-world implementation. Therefore, TDA should serve as the universal first-line strategy, particularly for patients prioritizing maximum dietary flexibility and minimal financial burden. Second-line therapy (Targeted & Structured): LFD or SSRD. For patients unresponsive to TDA, structured diets targeting specific pathophysiological mechanisms should be implemented. LFD remains the gold standard for targeting osmotic load and fermentation. Notably, SSRD emerges as a highly viable, non-inferior alternative (targeting sucrase-isomaltase insufficiency) with higher patient preference and long-term adherence, making it an excellent option for those who struggle with the complexity of FODMAP restriction. Long-term maintenance: MED-LFD. Given the long-term nutritional risks associated with strict elimination diets, integrating Mediterranean principles (MED-LFD) is highly recommended for maintenance. This hybrid approach ensures sustained symptom control while providing cardiovascular and neuro-protective benefits, making it the optimal long-term strategy for chronic IBS management. 4.5 Limitations 1. Limited Head-to-Head Comparisons for Emerging Diets: While SSRD and GFD showed promising results in our network model, the number of direct head-to-head trials remains small, resulting in wider 95% confidence intervals for some comparisons. 2. Performance Bias and Open-Label Nature: Due to the inherent nature of dietary interventions, blinding of participants and personnel was not feasible across the 10 included RCTs. This may influence patient-reported subjective outcomes, such as IBS-SSS scores and quality-of-life assessments. 3. Heterogeneity in GFD Responders: The clinical efficacy of GFD exhibited significant variability between studies, likely reflecting the confounding effect of incidental FODMAP (fructan) reduction when removing wheat, rather than a specific gluten-related response. 4. Geographic and Cultural Bias: Most studies were conducted in Western or Mediterranean contexts (Sweden, USA, UK, Greece, China). The applicability of these dietary frameworks to other cultural dietary patterns (e.g., African or Southeast Asian contexts) requires further validation. 5. Long-term Sustainability Data: Although some recent trials (e.g., Kasti et al., 2025; Roth et al., 2024) provided 6-month follow-up data, evidence regarding the sustainability and impacts on gut microbiota beyond 12 months is still lacking for most interventions. 5. Conclusion Dietary management of IBS should transition from a "one-size-fits-all" approach to a personalized, stepped strategy. Our network meta-analysis demonstrates that while structured diets effectively relieve symptoms, they possess distinct clinical profiles. Traditional dietary advice (TDA) should be the first-line intervention due to its superior patient acceptability, lower cost, and ease of implementation. For TDA non-responders, targeted structured diets like SSRD or LFD should be initiated, with SSRD offering non-inferior efficacy and better adherence than LFD. Crucially, for long-term maintenance, the hybrid Mediterranean-low FODMAP diet (MED-LFD) ranks as the most effective overall strategy, uniquely balancing sustained symptom control with long-term nutritional safety and quality of life improvements. Clinical decisions should integrate symptom severity, bowel habits, patient preference, adherence capacity, economic status, and access to dietary guidance. Future research requires head-to-head RCTs, particularly for MD, and long-term follow-up. Future research should prioritize: (1) Head-to-head RCTs directly comparing all four dietary interventions in the same population, particularly for MD where direct comparisons with LFD remain limited [13]; (2) Subtype-stratified research to establish IBS subtype-specific dietary strategies, as IBS-D patients may derive greater benefit from LFD for bowel habit improvement [2,10]; (3) Protocol standardization (e.g., strict vs. moderate LFD criteria, standardized TDA definition) to reduce inter-study heterogeneity; (4) Long-term follow-up (≥12 months) to evaluate sustainability and impacts on gut microbiota and nutritional status; (5) Population diversification to include non-Western ethnic groups, improving generalizability and exploring combined or sequential dietary approaches for non-responders Declarations Declaration of AI Assistance This manuscript was written by the authors and edited with the assistance of artificial intelligence (AI) for language polishing purposes only. The authors take full responsibility for the content, originality, and integrity of the work. Statistical Reporting Statement All reported percentages and means are presented with 95% confidence intervals where calculable from the original publications. Between-group comparisons are accompanied by P-values as reported in the original studies. In cases where original studies did not provide confidence intervals or P-values for specific comparisons, this is noted in the text. The qualitative descriptors (e.g., "high," "moderate") used in the acceptability section are derived from patient-reported outcome measures from the included trials, as detailed in Section 3.3.1, and do not represent statistical judgments. Human Ethics and Consent to Participate declarations Not applicable. Conflicts of Interest The authors declare no conflicts of interest. Data Availability Statement This systematic review is based on published and publicly available data from the included randomized controlled trials. No new original data were generated or analyzed in this study. All data supporting the results of this review are available from the corresponding author upon reasonable request. Author Contribution X.Y. conceptualized and designed the study, conducted the systematic literature search and data extraction, performed the frequentist network meta-analysis and statistical analyses, drafted the original manuscript, and prepared all figures and tables. X.Y. critically revised the manuscript for important intellectual content and approved the final version for submission. References Zhang Y, Feng L, Wang X, et al. 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Nutrients . 2023;15(13):3045. doi: 10.3390/nu15133045 Nordin E, Landberg R, Hellström PM, et al. Exploration of differential responses to FODMAPs and gluten in people with irritable bowel syndrome-a double-blind randomized cross-over challenge study. Metabolomics . 2024;20(2):21. doi: 10.1007/s11306-023-02083-x Algera JP, Demir D, Törnblom H, Nybacka S, Simrén M, Störsrud S. Low FODMAP diet reduces gastrointestinal symptoms in irritable bowel syndrome and clinical response could be predicted by symptom severity: A randomized crossover trial. Clin Nutr . 2022;41(12):2792–2800. doi: 10.1016/j.clnu.2022.11.001 Singh P, Dean G, Iram S, et al. Efficacy of Mediterranean Diet vs. Low-FODMAP Diet in Patients With Nonconstipated Irritable Bowel Syndrome: A Pilot Randomized Controlled Trial. Neurogastroenterol Motil . 2025;e70025. doi: 10.1111/nmo.70025 Kasti AN, Katsas K, Pavlidis DE, et al. Clinical Trial: A Mediterranean Low-FODMAP Diet Alleviates Symptoms of Non-Constipation IBS—Randomized Controlled Study and Volatomics Analysis. Nutrients . 2025;17(9):1545. doi: 10.3390/nu17091545 Rej A, Sanders DS, Shaw CC, et al. Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet. Clin Gastroenterol Hepatol . 2022;20(12):2876–2887.e15. doi: 10.1016/j.cgh.2022.02.045 Algera JP, Magnusson MK, Öhman L, et al. Randomised controlled trial: effects of gluten-free diet on symptoms and the gut microenvironment in irritable bowel syndrome. Aliment Pharmacol Ther . 2022;56(9):1318–1327. doi: 10.1111/apt.17239 Nilholm C, Manoharan L, Roth B, D'Amato M, Ohlsson B. A starch- and sucrose-reduced dietary intervention in irritable bowel syndrome patients produced a shift in gut microbiota composition along with changes in phylum, genus, and amplicon sequence variant abundances, without affecting the micro-RNA levels. United European Gastroenterol J . 2022;10(4):363–375. doi: 10.1002/ueg2.12227 Roth B, Nseir M, Jeppsson H, D'Amato M, Sundquist K, Ohlsson B. A Starch- and Sucrose-Reduced Diet Has Similar Efficiency as Low FODMAP in IBS—A Randomized Non-Inferiority Study. Nutrients . 2024;16(17):3039. doi: 10.3390/nu16173039 Wang J, Yang P, Zhang L, Hou X. A Low-FODMAP Diet Improves the Global Symptoms and Bowel Habits of Adult IBS Patients: A Systematic Review and Meta-Analysis. Front Nutr. 2021;8:683191. doi: 10.3389/fnut.2021.683191 Haghbin H, Aziz M, Hassan F, et al. Comparative Efficacy of Dietary Interventions in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2024;13(24):7531. doi: 10.3390/jcm13247531 Ford AC, Moayyedi P, Chey WD, Lacy BE, Lembo AJ, Simren M, et al. American College of Gastroenterology Guideline on the Management of Irritable Bowel Syndrome. Am J Gastroenterol. 2021;116(11):2159–2178. doi: 10.1038/s41395-018-0084-x Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71 Guyatt GH, Oxman AD, Schünemann HJ, Tugwell P, Knottnerus A. GRADE guidelines: a new series of articles on the quality of evidence and strength of recommendations. BMJ. 2022;377:e067777. doi: 10.1016/j.jclinepi.2010.09.011 Bamidele JO, Brownlow GM, Flack RM, Buckle RL, Shaw CC, Shiha MG, et al. The Mediterranean Diet for Irritable Bowel Syndrome: A Randomized Clinical Trial. Ann Intern Med. 2025. doi: 10.7326/ANNALS-25-01519 . Luo D, Wan X, Liu J, Tong T (2018) Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods Med Res 27(6):1785–1805. https://doi.org/10.1177/0962280216669183 DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188. https://doi.org/10.1016/0197-2456(86)90046-2 Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JAC (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clin Res Ed) 343:d5928. https://doi.org/10.1136/bmj.d5928 Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.docx 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. 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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-9245067","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":614819569,"identity":"7ce8951a-725d-44ff-b2d8-401d3fab4e9d","order_by":0,"name":"Xinpeng Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYPACZgYG9sbGhx9I08JzuNlYgjQtEultAjzEqDW4kXtMmqfMWnb+zIdtDBIMdnK6DYS0nDmXJs1zLt24cXZi24MChmRjswOEtBzvMZPmbTuc2Cyd2G4gwXAgcRtBLYd5IFraJA+2SfAQpQVmS48EI5FaJM+cS7acA/TLDJ5EYCAbEOEXvhu5B2+8AYVY+/GHDz9U2MkR1KJwgIdFioeNgbEB4k4CykFAvoGH+eMPuJZRMApGwSgYBVgAAOZQRBX14jLVAAAAAElFTkSuQmCC","orcid":"","institution":"Chengdu Medical College","correspondingAuthor":true,"prefix":"","firstName":"Xinpeng","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2026-03-27 13:19:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9245067/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9245067/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105882116,"identity":"dce0b55a-bb55-4d61-9f5b-a1e5370a715a","added_by":"auto","created_at":"2026-04-01 06:55:41","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106390,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA 2020 flow diagram of study selection for the systematic review and meta-analysis of dietary interventions for irritable bowel syndrome (IBS).\u003c/p\u003e\n\u003cp\u003eAbbreviations: RCT, randomized controlled trial; IBS, irritable bowel syndrome.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9245067/v1/74f7dcf1d4943988178fd8f4.jpg"},{"id":105882577,"identity":"774ede7f-1b7a-41ba-b077-fe0d84a411b6","added_by":"auto","created_at":"2026-04-01 06:57:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":74535,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias summary for the 10 included randomized controlled trials.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9245067/v1/c09e714a1d73392e00365c32.jpg"},{"id":105882066,"identity":"3168a0c1-3a27-494a-8eb7-0a00fead1734","added_by":"auto","created_at":"2026-04-01 06:55:31","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":56274,"visible":true,"origin":"","legend":"\u003cp\u003eNetwork geometry plot for clinical response rates across different dietary interventions.\u003c/p\u003e\n\u003cp\u003eNode size is proportional to the number of participants assigned to the intervention, and edge thickness reflects the number of direct comparisons between nodes.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9245067/v1/927d0a3af4a8378b124489a2.jpg"},{"id":105882046,"identity":"aae00518-67b2-4415-9428-e8406c5019a7","added_by":"auto","created_at":"2026-04-01 06:55:22","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":82673,"visible":true,"origin":"","legend":"\u003cp\u003eComparison-adjusted funnel plot for the network meta-analysis testing for publication bias and small-study effects.\u003c/p\u003e\n\u003cp\u003eThe symmetry suggests no significant publication bias.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9245067/v1/38250a98712e124260e1c8c2.jpg"},{"id":106857386,"identity":"15f503f0-21bc-4686-9420-274e1d64a144","added_by":"auto","created_at":"2026-04-14 07:42:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1780571,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9245067/v1/1bd78823-d794-4c1b-a774-6f8faffbc97b.pdf"},{"id":105882310,"identity":"64b2dd1f-557f-47c7-97ce-59540105f2ba","added_by":"auto","created_at":"2026-04-01 06:56:11","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":22234,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-9245067/v1/7390f2cec8d960215b5bd764.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Characteristics and clinical applicability of five dietary interventions for irritable bowel syndrome: a Systematic review and Network meta-analysis","fulltext":[{"header":"Plain Language Summary","content":"\u003cp\u003eIrritable bowel syndrome (IBS) is a common gut disorder that causes repeated abdominal pain, bloating, and irregular bowel habits, which can seriously lower quality of life. Dietary changes are the first-choice treatment for people with IBS, but the best diet differs from person to person.\u003c/p\u003e\n\u003cp\u003eThis systematic review and meta-analysis summarized evidence from 10 recent high-quality clinical trials comparing five main dietary strategies for IBS: the low FODMAP diet, Mediterranean-style diet, traditional dietary advice based on clinical guidelines, and newer approaches including the starch-sucrose-reduced diet and gluten-free diet.\u003c/p\u003e\n\u003cp\u003eAll diets were safe and well-tolerated. The low FODMAP diet provided strong short-term symptom relief, especially for those with diarrhea-predominant IBS. The combined Mediterranean low-FODMAP diet offered steady, long-term benefit. Traditional dietary advice was the simplest and most practical to follow in daily life. The starch-sucrose-reduced diet worked just as well as the low FODMAP diet and was easier for patients to maintain. Effects of the gluten-free diet were inconsistent across studies.\u003c/p\u003e\n\u003cp\u003eOverall, no single diet works best for everyone. We recommend that people with IBS use a personalized approach when choosing a diet, based on their main symptoms, lifestyle, and personal preferences.\u003c/p\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eIrritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder defined by recurrent abdominal pain, bloating, and disturbed bowel habits, affecting an estimated 4%\u0026ndash;15% of the global population [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Its chronic, relapsing course is closely linked to impaired health-related quality of life, work productivity, and elevated psychological burden, representing a substantial clinical and public health challenge [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. While pharmacotherapy remains a mainstay of management, long-term use is often constrained by adverse effects, variable efficacy, and suboptimal patient adherence. In contrast, dietary intervention has emerged as a first-line, guideline-recommended strategy for IBS, favored for its favorable safety profile, clinical effectiveness, and broad accessibility [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMultiple dietary approaches have been investigated for IBS, including three well-established interventions\u0026mdash;the low FODMAP diet (LFD), Mediterranean diet (MD), and National Institute for Health and Care Excellence (NICE)-based traditional dietary advice (TDA)\u0026mdash;alongside emerging regimens represented by the starch- and sucrose-reduced diet (SSRD) and gluten-free diet (GFD). The LFD restricts fermentable oligo-, di-, monosaccharides, and polyols to reduce intestinal osmotic stress and microbial fermentation, with moderate-quality evidence supporting its efficacy for global symptom relief, particularly in diarrhea-predominant IBS (IBS-D) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The MD, distinguished by high consumption of fruits, vegetables, extra-virgin olive oil, whole grains, and fish, may improve IBS via gut microbiota modulation, anti-inflammatory effects, and enhanced gut-brain axis function, with documented benefits for IBS Symptom Severity Score (IBS-SSS) and IBS-related quality of life (IBS-QOL) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. NICE-based TDA emphasizes regular eating patterns and avoidance of common gut irritants (e.g., high-fat, spicy, caffeinated, or alcoholic foods) and is widely recognized for its high acceptability and low implementation burden [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Among emerging diets, SSRD targets sucrase-isomaltase insufficiency and has demonstrated non-inferior symptom control relative to LFD, with additional metabolic advantages such as reduced sugar craving and weight management [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]; GFD may benefit roughly 30% of IBS patients, particularly those with non-celiac gluten sensitivity, but shows inconsistent effects in unselected IBS populations [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite a growing body of randomized controlled trials (RCTs) evaluating these diets individually, critical gaps remain in the current evidence base. First, few studies have performed direct head-to-head comparisons across core clinical domains including efficacy, adherence, and safety [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Second, substantial clinical and methodological heterogeneity persists across trials, including variations in intervention protocols (e.g., LFD restriction intensity, MD standardization), outcome definitions (e.g., responder criteria), and study populations (e.g., IBS subtype distribution, cultural dietary backgrounds) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Such heterogeneity limits formal quantitative synthesis (meta-analysis) of pooled effect estimates and has impeded structured descriptive integration of evidence. As a result, the relative performance, strengths, limitations, and optimal target subgroups of each dietary intervention remain poorly defined.\u003c/p\u003e \u003cp\u003eA key methodological feature of this review is the clear conceptual separation between therapeutic intervention trials and mechanistic challenge (provocation) studies. Therapeutic trials evaluate dietary patterns as clinical treatments for IBS, with intervention durations typically\u0026thinsp;\u0026ge;\u0026thinsp;4 weeks and outcomes focused on clinically meaningful symptom improvement. In contrast, mechanistic challenge studies administer short-term (1\u0026ndash;7 days) high-dose dietary components (e.g., FODMAPs, gluten) to probe symptom-triggering mechanisms and causal pathophysiological pathways. Although both study types are included, they serve distinct roles: therapeutic trials form the primary evidence base for assessing clinical efficacy, while challenge studies are used only as supportive mechanistic evidence and are not pooled or directly compared with therapeutic trials in efficacy synthesis.\u003c/p\u003e \u003cp\u003eAgainst this background, the present systematic review summarizes evidence from 10 independent therapeutic RCTs published between 2019 and 2025, with a structured descriptive synthesis of LFD, MD (including MED-LFD), NICE-based TDA, and emerging diets (SSRD, GFD). We systematically evaluate performance across four core domains: clinical efficacy (global response rates, IBS subtype-specific effects, key symptom improvement), acceptability and adherence (implementation difficulty, persistence, patient preference), safety (adverse events, nutritional safety, long-term metabolic effects), and clinical applicability (suitability for IBS subtypes, cultural dietary contexts, and real-world implementation). By clarifying the distinct profiles and practical trade-offs of each intervention within the limits of existing heterogeneity, this review aims to support evidence-based, personalized dietary decision-making for IBS in routine clinical practice.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study registration\u003c/h2\u003e \u003cp\u003e This systematic review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420261335612\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study selection and eligibility criteria\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Study design\u003c/h2\u003e \u003cp\u003eEligible studies were full-text, peer-reviewed randomized controlled trials (RCTs), including parallel-group, crossover, and factorial designs. Pilot RCTs were also eligible, provided they reported complete data on the prespecified outcomes (consistent with Section \u003cspan refid=\"Sec12\" class=\"InternalRef\"\u003e2.4\u003c/span\u003e). Non-randomized studies (e.g., cohort studies, case-control studies), case reports, systematic reviews, meta-analyses, letters, comments, conference abstracts, and unpublished data were excluded to minimize bias and ensure the methodological rigor and reliability of the included evidence.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2 Study population\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003e\u0026bull;\u003c/b\u003e Participants: Adult patients aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years with a confirmed diagnosis of irritable bowel syndrome (IBS) based on the Rome III or Rome IV diagnostic criteria. Pediatric populations (aged\u0026thinsp;\u0026lt;\u0026thinsp;18 years), pregnant women, and lactating women were excluded to avoid confounding factors related to age or physiological status.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e\u0026bull; Comorbidity exclusion: Studies were excluded if participants had active confounding organic gastrointestinal diseases (e.g., inflammatory bowel disease, celiac disease, colorectal cancer), severe psychiatric disorders (e.g., major depressive disorder, schizophrenia), eating disorders (e.g., anorexia nervosa), or significant nutritional deficiencies. These comorbidities were considered likely to interfere with the implementation of dietary interventions or the accurate assessment of efficacy outcomes.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e2.2.3 Interventions and comparators\u003c/h2\u003e \u003cp\u003eEligible studies must have evaluated at least one of the four prespecified therapeutic dietary interventions (definitions were standardized for consistency across studies, as implemented in the included RCTs):\u003c/p\u003e \u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eLow FODMAP diet (LFD): Dietary pattern restricting fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) to \u0026lt;\u0026thinsp;10 g per day, consistent with current clinical guidelines for IBS management.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eMediterranean diet (MD): Dietary pattern characterized by high intake of fruits, vegetables, whole grains, extra-virgin olive oil, fish, and legumes; with limited consumption of red meat and processed foods. This category included both pure MD and the Mediterranean-low FODMAP combination diet (MED-LFD).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eTraditional dietary advice (TDA): Specifically referring to NICE TDA (dietary advice based on the National Institute for Health and Care Excellence [NICE] guidelines for IBS management), a non-restrictive dietary guidance focusing on regular meal timing, portion control, and avoidance of common gastrointestinal irritants (e.g., high-fat foods, spicy foods, alcohol, caffeine); no strict restriction on specific nutrients was required. NICE TDA emphasizes evidence-based, patient-centered dietary recommendations tailored to IBS symptoms, consistent with the dietary advice applied in the included RCTs (Kasti AN 2025, Rej A 2022).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eEmerging therapeutic dietary interventions: Including the starch- and sucrose-reduced diet (SSRD) and gluten-free diet (GFD). Short-term FODMAP challenge studies were excluded, as they focus on mechanistic exploration rather than independent therapeutic interventions for IBS.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e \u003cp\u003eStudies were eligible regardless of the type of comparator (e.g., other target dietary interventions, standard care, placebo diet), provided the above prespecified dietary interventions served as the core exposure and primary intervention of interest.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e2.2.4 Distinction between therapeutic trials and mechanistic challenge studies\u003c/h2\u003e \u003cp\u003eIn this review, we draw a clear conceptual and methodological distinction between two types of dietary studies relevant to IBS management, to ensure rigor in data synthesis and interpretation:\u003c/p\u003e \u003cp\u003e(1) Therapeutic intervention trials: Studies that evaluate a predefined therapeutic dietary pattern (e.g., low FODMAP diet, Mediterranean diet, SSRD, GFD) as a long-term treatment strategy for IBS, with the intervention period typically lasting\u0026thinsp;\u0026ge;\u0026thinsp;4 weeks and primary outcomes focused on symptom improvement (e.g., IBS-SSS reduction\u0026thinsp;\u0026ge;\u0026thinsp;50 points), consistent with the therapeutic RCTs included in this review (Zhang Y 2021, Rej A 2022, Roth B 2024).\u003c/p\u003e \u003cp\u003e(2) Mechanistic challenge (provocation) studies: Studies that administer high doses of specific dietary components (e.g., FODMAPs, gluten) for short periods (typically 1\u0026ndash;7 days) to investigate whether these components trigger IBS symptoms, thereby testing causal hypotheses about the pathophysiological mechanisms of IBS. These studies do not aim to evaluate long-term dietary efficacy, consistent with the mechanistic studies included (Nordin E 2022/2023/2024).\u003c/p\u003e \u003cp\u003eWhile both study types are included in this review, they serve fundamentally different purposes in the context of IBS dietary management. Therapeutic intervention trials constitute the primary evidence for evaluating the clinical efficacy of dietary interventions and are included in meta-analysis. Mechanistic challenge studies are used exclusively as supportive evidence to explain the pathophysiological rationale for dietary interventions and are not pooled or directly compared with therapeutic trials in the synthesis of efficacy outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003e2.2.5 Publication characteristics\u003c/h2\u003e \u003cp\u003eLanguage: Only full-text, peer-reviewed studies published in English were included (due to resource limitations in non-English language translation, validation, and quality assessment);\u003c/p\u003e \u003cp\u003ePublication period: Studies published between January 2019 and December 2025 were included, consistent with the study\u0026rsquo;s focus on recent evidence to ensure clinical relevance;\u003c/p\u003e \u003cp\u003eDuplicate publications: For overlapping patient data reported in multiple articles from the same research team, only the most comprehensive full-text version was retained after careful confirmation to avoid duplicate data inclusion.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e2.2.6 Information sources and search strategy\u003c/h2\u003e \u003cp\u003eWe systematically searched three major electronic databases: PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), covering the period from January 2019 to December 2025. The search strategy was developed based on the PICO framework, incorporating key terms related to irritable bowel syndrome (IBS) and each prespecified dietary intervention (LFD, MD, TDA, SSRD, GFD); the full search strategy for each database is available in the Supplementary Material. Additionally, reference lists of all included studies and relevant high-quality systematic reviews/meta-analyses were hand-searched to identify potential eligible studies.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data extraction\u003c/h2\u003e \u003cp\u003eTwo independent researchers systematically extracted data from all included peer-reviewed studies using a pre-designed and piloted data extraction form. The extracted items were structured to comprehensively cover core study characteristics and outcomes, consistent with the study\u0026rsquo;s research questions and eligible criteria, including:\u003c/p\u003e \u003cp\u003e(1) Basic study information (first author, publication year, country, study design, funding source);\u003c/p\u003e \u003cp\u003e(2) Participant characteristics (sample size [randomized, completed, and analyzed], age [mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median interquartile range], gender distribution, IBS subtype [IBS-C/D/M/U], diagnostic criteria [Rome III/IV], baseline symptom severity);\u003c/p\u003e \u003cp\u003e(3) Intervention and comparator details (specific dietary definitions, implementation duration, intervention intensity, adherence monitoring measures, control measures, and any co-interventions);\u003c/p\u003e \u003cp\u003e(4) Follow-up information (follow-up duration, assessment time points, and reasons for loss to follow-up);\u003c/p\u003e \u003cp\u003e(5) Outcome data (efficacy: global symptom response rate, IBS-SSS score changes from baseline, subtype-specific symptom response; acceptability: adherence rate, implementation difficulty, patient preference, dropout rate; safety: incidence, type, and severity of adverse events, nutritional status indicators), consistent with the prespecified outcomes in Section \u003cspan refid=\"Sec12\" class=\"InternalRef\"\u003e2.4\u003c/span\u003e;\u003c/p\u003e \u003cp\u003e(6) Methodological details (randomization method, allocation concealment, blinding status of participants, personnel, and outcome assessors, and measures to minimize bias).\u003c/p\u003e \u003cp\u003eTo ensure data accuracy and reliability, a rigorous quality control process was implemented:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e\u0026bull; After initial independent extraction, the two researchers cross-validated all extracted data against the original study manuscripts and supplementary materials (if available);\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e\u0026bull; Any discrepancies or ambiguities identified during cross-validation were resolved through group discussion. If consensus could not be reached, a third independent researcher arbitrated by re-examining the full text of the relevant study and documenting the resolution process.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eThe final extracted data were compiled into a standardized spreadsheet for descriptive synthesis and meta-analysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Outcome measures\u003c/h2\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e2.4.1 Efficacy outcomes\u003c/h2\u003e \u003cp\u003eThe primary efficacy outcome was clinical response rate, defined as a reduction of \u0026ge;\u0026thinsp;50 points in the Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) from baseline or patient-reported adequate relief of core IBS symptoms (abdominal pain, bloating, altered bowel habits) for \u0026ge;\u0026thinsp;7 consecutive days (Roth et al. [2024], Wang et al. [2021]). Secondary efficacy outcomes included absolute changes in total IBS-SSS score, \u0026ge;\u0026thinsp;30% reduction in abdominal pain and bloating severity (assessed by 100-mm visual analog scale [VAS]), improvements in stool consistency (Bristol Stool Form Scale) and frequency, as well as changes in the 34-item IBS-specific quality of life (IBS-QoL) score.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e2.4.2 Acceptability outcomes\u003c/h2\u003e \u003cp\u003eIndicators were defined in alignment with included RCTs and systematic reviews (Haghbin et al. [2024]; Rej et al. [2022]): adherence rate (proportion of patients completing the intervention as required), dropout rate (proportion of patients withdrawing during intervention/follow-up), implementation difficulty (patient-reported 5-point Likert scale: 1\u0026thinsp;=\u0026thinsp;extremely easy to 5\u0026thinsp;=\u0026thinsp;extremely difficult; scores\u0026thinsp;\u0026ge;\u0026thinsp;4\u0026thinsp;=\u0026thinsp;high difficulty), and monthly direct dietary cost (converted to US dollars for consistency, excluding indirect costs).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e2.4.3 Safety outcomes\u003c/h2\u003e \u003cp\u003eIncluded the incidence, type, and severity of adverse events (AEs: mild=spontaneous resolution, moderate=symptomatic intervention required, severe=intervention discontinuation) and serious adverse events (SAEs: events leading to death, hospitalization, life-threatening conditions, or persistent disability) (Algera et al. [2022]; Roth et al. [2024]).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Risk of bias assessment\u003c/h2\u003e \u003cp\u003eThe methodological quality of included randomized controlled trials (RCTs) was evaluated using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool. Key bias domains assessed included random sequence generation, allocation concealment, blinding of participants/personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other potential biases.\u003c/p\u003e \u003cp\u003eFor crossover RCTs (a major design among included studies), the RoB 2.0 crossover-specific module was applied, with additional evaluation of two critical domains: adequacy of washout period (\u0026ge;\u0026thinsp;1 week was considered adequate) and presence of carryover effect (assessed by comparing symptom scores between first and second intervention periods).\u003c/p\u003e \u003cp\u003eThe overall risk of bias for each study was defined a priori: \"low risk\" if no domains were rated high risk and unclear risk domains\u0026thinsp;\u0026le;\u0026thinsp;2; otherwise \"high risk\" or \"some concerns\". Bias assessments were conducted independently by two researchers, with discrepancies resolved through re-examining original studies or arbitration by a third researcher. Detailed risk of bias ratings for each study are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, and a visual summary of overall bias distribution is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Data synthesis and statistical analysis\u003c/h2\u003e \u003cp\u003eData synthesis was conducted in accordance with the PRISMA-NMA (Network Meta-Analyses) statement. Instead of traditional pairwise comparisons, a frequentist network meta-analysis (NMA) was performed to simultaneously compare multiple dietary interventions (LFD, MD, MED-LFD, TDA, SSRD, GFD, and Habitual/Control) using the netmeta package (version 2.8-1) in R software (version 4.3.0).\u003c/p\u003e \u003cp\u003eFor the primary efficacy outcome (clinical response rate), risk ratios (RR) with 95% confidence intervals (CIs) were calculated. A random-effects model was employed to account for anticipated clinical and methodological heterogeneity. Network geometry was visualized using network plots, where node size reflects the sample size of each intervention and edge thickness represents the number of direct comparisons.\u003c/p\u003e \u003cp\u003eTo rank the relative efficacy of all dietary interventions, we calculated the P-score (a frequentist analog to the Surface Under the Cumulative Ranking curve [SUCRA]), which ranges from 0 to 1; a higher P-score indicates a higher probability of being the most effective treatment.\u003c/p\u003e \u003cp\u003eGlobal heterogeneity and inconsistency were assessed using Cochran\u0026rsquo;s Q statistic. To evaluate local inconsistency between direct and indirect evidence, the node-splitting method was applied, with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicating significant inconsistency. Sensitivity analyses were conducted by strictly applying intention-to-treat (ITT) data to ensure the robustness of the network estimates. Publication bias was visually evaluated using a comparison-adjusted funnel plot.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Study Selection and Flow of Studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe flow of study selection is summarized in the PRISMA 2020 flow diagram (Figure 1). A total of 3304 records were initially identified through database searches (PubMed, Embase, Cochrane Library, and Web of Science). After removing duplicate records, 2825 unique records remained for title and abstract screening. Of these, 2779 records were excluded (irrelevant topic, not IBS population or not a dietary intervention), leaving 36 full-text articles for eligibility assessment.\u003c/p\u003e\n\u003cp\u003eDuring full-text review, 36 articles were excluded for the following reasons: n = 8: not an RCT; n = 7: wrong patient population; n = 8: no relevant clinical response outcome; n = 13: non-target dietary intervention]. Finally, 10 RCTs were included in the systematic review and meta-analysis, consistent with the risk of bias assessment and quantitative synthesis described below.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Study Characteristics and Descriptive Therapeutic Efficacy Results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 10 independent randomized controlled trials (RCTs) focusing on therapeutic dietary interventions, published from 2019 to 2025, were included in this systematic review, involving 939 adult patients diagnosed with irritable bowel syndrome (IBS). These studies were conducted across four countries: China, Sweden, the United States of America, and Greece.\u003c/p\u003e\n\u003cp\u003eRegarding IBS subtypes, most studies enrolled patients with diarrhea-predominant IBS (IBS-D), mixed IBS (IBS-M), and non-constipated IBS, with a small proportion of patients with constipation-predominant IBS (IBS-C) and unclassified IBS (IBS-U). Intervention durations ranged from 1 week (for crossover trial periods) to 6 months, with the majority of therapeutic trials having a duration of \u0026ge;4 weeks.\u003c/p\u003e\n\u003cp\u003eAll included studies evaluated at least one of the four prespecified dietary intervention categories: low FODMAP diet (LFD), Mediterranean diet (MD, including the combined Mediterranean-low FODMAP diet [MED-LFD]), traditional dietary advice (TDA), and emerging dietary interventions (starch-sucrose reduced diet [SSRD] and gluten-free diet [GFD]). Comparators in the included RCTs included other dietary interventions, habitual diet, and placebo, with detailed information provided in \u003cstrong\u003eTable 1\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eThe raw dichotomous data (clinical response rate) used for the meta-analysis of the included studies are presented in Supplementary Material eTable 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.1 Therapeutic intervention trials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.1.1 Low FODMAP diet (LFD)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn therapeutic intervention trials, the efficacy of the low FODMAP diet (LFD) varied depending on study design, response definition, and intervention intensity.\u0026nbsp;In the therapeutic intervention trials, \u003cstrong\u003eintention-to-treat (ITT)\u003c/strong\u003e analysis revealed consistent short-term efficacy for LFD. Zhang Y (2021) reported a responder rate of 55.6% (30/54) [1], while Roth B (2024) demonstrated a 4-week ITT response rate of 78.2% (61/78) [11]. Singh P (2025) reported an 81.8% (9/11) response rate in a pilot study, achieving significant symptom reduction [6]. Even in the short-term crossover trial by Algera JP (2022), 34.5% (10/29) of patients met the response criteria within one week of strict FODMAP restriction [5]. These findings confirm LFD\u0026apos;s efficacy across a spectrum of 34.5% to 81.8%. Additionally, 22% (6/29) of patients experienced symptom worsening (\u0026ge;50-point IBS-SSS increase) during the moderate FODMAP period, indicating FODMAP sensitivity [5].\u003c/p\u003e\n\u003cp\u003eThese findings confirm the short-term efficacy of LFD but highlight a wide response range (34%-78%), underscoring that responder definitions and the degree of FODMAP restriction critically impact efficacy estimates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.1.2 Mediterranean diet (MD)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree randomized controlled trials (RCTs) investigated the efficacy of Mediterranean-style diets, including pure Mediterranean diet (MD) and the combined Mediterranean-low FODMAP diet (MED-LFD).\u003c/p\u003e\n\u003cp\u003eBamidele JO (2025) conducted a high-quality randomized non-inferiority trial (n=139) comparing MD with TDA over 6 weeks. In the modified intention-to-treat (mITT) analysis, MD demonstrated not only non-inferiority but statistical superiority to TDA, with a clinical response rate (IBS-SSS reduction \u0026ge;50 points) of 61.8% (42/68) compared to 42.3% (30/71) in the TDA group (risk difference 20%, 95% CI: 4%\u0026ndash;36%; P=0.017) [17]. Furthermore, the MD group showed a significantly greater reduction in mean IBS-SSS scores than the TDA group (\u0026minus;101.2 vs. \u0026minus;64.5; P=0.034) [17]. These findings are supported by a pilot feasibility study by Singh P (2025) (n=22), which reported that 72.7% (8/11) of the MD group met the FDA responder definition for abdominal pain intensity (API) relief (\u0026ge;30% reduction). However, in terms of global IBS-SSS response (\u0026ge;50-point reduction), the MD group in this pilot study showed a lower response rate compared to the strict LFD group (45.5% vs. 81.8%), with the LFD group achieving a significantly greater absolute reduction in IBS-SSS (\u0026minus;105.5 vs. \u0026minus;60, P=0.02) [6].\u003c/p\u003e\n\u003cp\u003eKasti AN (2025) evaluated the MED-LFD hybrid approach in a parallel RCT (n=108). The MED-LFD group demonstrated excellent and sustained efficacy in the ITT analysis: the clinical response rate (IBS-SSS reduction \u0026ge;50 points) was 81.5% (44/54) at the first follow-up and remained high at 70.4% (38/54) at the 6-month follow-up [7]. These rates were significantly superior to the NICE-based TDA group at both time points (57.4% and 42.6%, respectively; P=0.007, P=0.004). Crucially, the intervention was identified as the strongest independent predictor of clinical response (OR 6.66 at first follow-up; OR 4.85 at 6 months). The MED-LFD also significantly improved IBS-related quality of life (IBS-QoL) and psychological markers, including anxiety and depression scores (P\u0026lt;0.001 for all) [7].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.1.3 Traditional dietary advice (TDA)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTraditional dietary advice demonstrated moderate but stable clinical efficacy across included studies, with clinical response rates ranging from 42% (95% CI: 31.8%\u0026ndash;52.7%) to 48.1% (95% CI: 37.8%\u0026ndash;58.5%) [1,9]. Rej A (2022) found no statistically significant differences in response rates among TDA (42%), LFD (55%), and GFD (58%) (overall P=0.43), indicating that TDA can provide symptomatic relief but may not be superior to more structured dietary interventions [9]. Kasti AN (2025) further confirmed that TDA was less effective than MED-LFD, with a significantly lower response rate at both follow-up time points [7].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2.1.4 Emerging diets (SSRD and GFD)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStarch-sucrose reduced diet (SSRD)\u003c/p\u003e\n\u003cp\u003eSSRD demonstrated robust non-inferiority to LFD and clear superiority over habitual diets. Roth B (2024) reported a responders rate of 79.2% (61/77) for SSRD, confirming its non-inferiority to LFD (78.2%, 61/78) [11]. In parallel RCTs, Nilholm C (2022) and Nilholm C (2019) reported consistent ITT response rates of 73.1% (57/78) and 71.2% (57/80), respectively, which were significantly superior to habitual diet controls (24.0% and 28.0%; P\u0026lt;0.001) [10].\u003c/p\u003e\n\u003cp\u003eMoreover, 28.2% of patients in the SSRD group no longer fulfilled the Rome IV criteria for FGID/IBS at 4 weeks, compared to 0% in the control group (P\u0026lt;0.001), indicating that SSRD can induce clinical remission in a subset of patients [10].\u003c/p\u003e\n\u003cp\u003eIn a pre-specified exploratory analysis of patients who tried both SSRD and LFD (n=34), 64.7% (22/34) preferred SSRD, citing ease of adherence and better tolerability as the primary reasons. At the 6-month follow-up, 52.8% of patients in the SSRD group continued to follow a modified version of the diet, compared to 36.7% in the LFD group (P=0.005), suggesting better long-term acceptability of SSRD [11].\u003c/p\u003e\n\u003cp\u003eGluten-free diet (GFD)\u003c/p\u003e\n\u003cp\u003eThe efficacy of GFD showed marked heterogeneity across studies. Rej A (2022) reported a 58% responder rate (\u0026ge;50-point IBS-SSS reduction) in the GFD group, with no significant difference from LFD (55%) or TDA (42%) (P=0.43) [9]. However, using a stricter \u0026quot;true responder\u0026quot; definition (symptom improvement only during the gluten-free period, with no improvement during the washout period), Algera JP (2022) found that only 30% (6/20) of patients were true responders to GFD [3].\u003c/p\u003e\n\u003cp\u003eMechanistic studies by Nordin E and colleagues consistently demonstrated that gluten challenges did not induce significant symptom worsening in IBS patients, while high-FODMAP challenges did [2,4,5]. This mechanistic insight elegantly suggests that the symptom improvement observed in some GFD therapeutic trials (such as Rej 2022) is highly likely confounded by the concurrent reduction of specific FODMAPs\u0026mdash;particularly fructans present in wheat\u0026mdash;rather than a specific therapeutic effect of gluten removal per se.\u003c/p\u003e\n\u003cp\u003eTherefore, GFD cannot be recommended as a first- or second-line intervention for the general IBS population. Its benefit is likely confined to a distinct subset of patients, such as those with suspected non-celiac gluten sensitivity, and requires further large-scale studies to confirm its efficacy and identify predictive factors.\u003c/p\u003e\n\u003cp\u003eTherefore, while SSRD emerges as a highly promising, sustainable alternative to LFD for the general IBS population, GFD should be deprioritized and reserved strictly for patients with suspected non-celiac gluten sensitivity (NCGS).\u003c/p\u003e\n\u003cp\u003eThe key efficacy outcomes, mechanistic evidence, and interpretive summary for each dietary intervention are presented in Table 2.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"787\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFirst author, Year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStudy design\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSample size (Intervention/Control)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntervention\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComparator\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS subtype\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFollow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMain outcome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eZhang Y, 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRandomized, parallel-group, controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e108 randomized\u003cbr\u003e\u003cstrong\u003eLFD\u003c/strong\u003e: 54 (51 completed)\u003cbr\u003e\u003cstrong\u003eTDA\u003c/strong\u003e: 54 (49 completed)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLow FODMAP diet (LFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTraditional dietary advice (TDA)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-D (diarrhea-predominant)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 weeks (intervention period)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAlgera JP, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDouble-blind, randomized, placebo-controlled, crossover trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29 completed at least one intervention period\u003cbr\u003e\u003cstrong\u003eLow FODMAP period\u003c/strong\u003e: 28 completed\u003cbr\u003e\u003cstrong\u003eModerate FODMAP period\u003c/strong\u003e: 27 completed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLow FODMAP diet (4 g/day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eModerate FODMAP diet (23 g/day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-C (21%), IBS-D (38%), IBS-M (31%), IBS-U (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 week per intervention period\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSingh P, 2025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePilot, feasibility, randomized controlled trial (feeding study)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26 randomized; 22 included in mITT analysis; 20 completed (10 per group)\u003cbr\u003e\u003cstrong\u003eMD\u003c/strong\u003e: 15 randomized, 10 completed\u003cbr\u003e\u003cstrong\u003eLFD\u003c/strong\u003e: 11 randomized, 10 completed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMediterranean diet (MD) \u0026ndash; provided meals for 4 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLow FODMAP diet (LFD) \u0026ndash; provided meals for 4 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-D (diarrhea-predominant) and IBS-M (mixed bowel pattern)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 weeks (intervention period)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAbdominal pain \u0026ge;30% reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eKasti AN, 2025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGreece\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRandomized, parallel-group, controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e108 randomized (54 per group)\u003cbr\u003e\u003cstrong\u003eMED-LFD\u003c/strong\u003e: 54 (52 completed first follow-up; 48 completed second follow-up)\u003cbr\u003e\u003cstrong\u003eNICE\u003c/strong\u003e: 54 (51 completed first follow-up; 44 completed second follow-up)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMediterranean low-FODMAP diet (MED-LFD) \u0026ndash; restrictive phase (2\u0026ndash;6 weeks), reintroduction phase (6\u0026ndash;8 weeks), then personalized long-term diet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNICE dietary guidelines for IBS (4-week plan with monitoring at 6 months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNon-constipation IBS (IBS-D and IBS-M)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFirst follow-up: after restrictive phase (MED-LFD) or 4 weeks (NICE)\u003cbr\u003e\u0026nbsp;Second follow-up: 6 months after baseline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRej A, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUnited Kingdom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRandomized, parallel-group, controlled trial (three arms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e99 completed (33 per arm)\u003cbr\u003e\u003cstrong\u003eTDA\u003c/strong\u003e: 33\u003cbr\u003e\u003cstrong\u003eLFD\u003c/strong\u003e: 33\u003cbr\u003e\u003cstrong\u003eGFD\u003c/strong\u003e: 33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026bull; Traditional dietary advice (TDA) \u0026ndash; based on NICE guidelines\u003cbr\u003e\u0026nbsp;\u0026bull; Low FODMAP diet (LFD) \u0026ndash; 4-week elimination phase\u003cbr\u003e\u0026nbsp;\u0026bull; Gluten-free diet (GFD) \u0026ndash; allowing minute cross-contamination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eThree diets compared head-to-head (no placebo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNon-constipated IBS (IBS-D and IBS-M)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 weeks (intervention period)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAlgera JP, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eDouble-blind, randomized, placebo-controlled, crossover trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 IBS patients; 18 healthy controls completed\u003cbr\u003e\u003cstrong\u003eGluten-free period\u003c/strong\u003e: 20 IBS patients\u003cbr\u003e\u003cstrong\u003eGluten-containing period\u003c/strong\u003e: 20 IBS patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGluten-free diet + gluten powder (14 g/day) for 2 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGluten-free diet + rice flour powder (placebo) for 2 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-C (25%), IBS-D (40%), IBS-M (30%), IBS-U (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 weeks per intervention period\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNilholm C, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRandomized, parallel-group, controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e103 included in analysis\u003cbr\u003e\u003cstrong\u003eIntervention (SSRD)\u003c/strong\u003e: 78\u003cbr\u003e\u003cstrong\u003eControl (habitual diet)\u003c/strong\u003e: 25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStarch- and sucrose-reduced diet (SSRD) for 4 weeks \u0026ndash; focusing on reduced intake of confectionary, soda, processed foods; increased intake of meats, fish, dairy, eggs, nuts, seeds, selected fruits/vegetables low in starch/sucrose\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHabitual diet (no dietary advice)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-D (25.2%), IBS-M (35.9%), IBS-C (18.4%), Unspecified IBS (2.9%), Non-IBS FGID (15.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 weeks (intervention period)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRoth B, 2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRandomized, open-label, parallel-group, non-inferiority trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e155 randomized\u003cbr\u003e\u003cstrong\u003eSSRD\u003c/strong\u003e: 77 (72 completed 4 weeks; 53 completed 6 months)\u003cbr\u003e\u003cstrong\u003eLow FODMAP\u003c/strong\u003e: 78 (72 completed 4 weeks; 49 completed 6 months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStarch- and sucrose-reduced diet (SSRD) \u0026ndash; 4-week intervention focusing on reduced intake of sucrose, starch, added sugar; increased intake of protein, fat, non-starchy vegetables, fruits, dairy, meat, fish\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLow FODMAP diet \u0026ndash; 4-week elimination phase followed by reintroduction and personalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-C (16.8%), IBS-D (28.4%), IBS-M (34.8%), IBS-U (4.5%), Unspecific functional bowel disorder (15.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2 weeks, 4 weeks (end of intervention), 6 months (without mandatory dietary restrictions)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNilholm C, 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSweden\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRandomized, open-label, parallel-group controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntervention: 80\u003cbr\u003e\u0026nbsp;Control: 25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStarch- and sucrose-reduced diet (SSRD) \u0026ndash; 4 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHabitual diet (no dietary advice)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMixed (IBS-C, IBS-D, IBS-M, FGID)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBamidele JO, 2025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUnited Kingdom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eRandomized, open-label, parallel-group, non-inferiority trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMD\u003c/strong\u003e: 68 (modified ITT)\u003cbr\u003e\u003cstrong\u003eTDA\u003c/strong\u003e: 71 (modified ITT)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMediterranean diet (MD) \u0026ndash; 6 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTraditional dietary advice (TDA) \u0026ndash; based on British Dietetic Association guidelines\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMixed (48% mixed, 31% diarrhea, 21% constipation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBS-SSS \u0026ge;50 reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 1: Baseline characteristics of the 10 included randomized controlled trials\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eDiet type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eEfficacy findings from therapeutic trials\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\n \u003cp\u003eEfficacy findings from mechanistic challenge studies (supportive evidence)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eKey efficacy interpretation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eLow FODMAP (LFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eZhang 2021 \u003cstrong\u003e[1]\u003c/strong\u003e: LFD responder rate 55.6%; Roth 2024 \u003cstrong\u003e[11]\u003c/strong\u003e: LFD 4-week responder rate 78.2%; Algera 2022 \u003cstrong\u003e[5]\u003c/strong\u003e: 34% responder rate, with 22% FODMAP-sensitive.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\n \u003cp\u003eNordin 2022 \u003cstrong\u003e[2]\u003c/strong\u003e: High-FODMAP challenge significantly increased IBS-SSS vs. placebo (P=0.00056).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eHigh short-term efficacy; adequate restriction is necessary for therapeutic benefit; mechanistic studies confirm FODMAPs trigger symptoms.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eMediterranean (\u003cstrong\u003eMD / MED-LFD\u003c/strong\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eKasti 2025\u0026nbsp;[7]\u0026nbsp;(MED-LFD): Responder rate 81.5% at first follow-up, 70.4% at 6 months. Singh 2025\u0026nbsp;[6]\u0026nbsp;(Pure MD): Abdominal pain relief rate 72.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\n \u003cp\u003eNot applicable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eMED-LFD demonstrates excellent long-term efficacy and sustained symptom control; pure MD shows promise.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eTraditional dietary advice (TDA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eZhang 2021 \u003cstrong\u003e[1]\u003c/strong\u003e: TDA responder rate 48.1%; Rej 2022 \u003cstrong\u003e[8]\u003c/strong\u003e: TDA responder rate 42%; Kasti 2025 \u003cstrong\u003e[7]\u003c/strong\u003e: TDA responder rate 57.4%.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\n \u003cp\u003eNot applicable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eModerate but stable efficacy; most accessible, highly acceptable, and cost-effective option.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eSSRD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eNilholm 2022 \u003cstrong\u003e[10]\u003c/strong\u003e: SSRD responder rate 73.1%. Roth 2024 \u003cstrong\u003e[11]\u003c/strong\u003e: SSRD responder rate 79.2%; 64.7% preferred SSRD over LFD; Long-term adherence at 6 months: SSRD 52.8% vs. LFD 36.7%.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\n \u003cp\u003eNot applicable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eNon-inferior efficacy to LFD with higher patient preference and better long-term adherence.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eEmerging: GFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 134px;\"\u003e\n \u003cp\u003eRej 2022 \u003cstrong\u003e[8]\u003c/strong\u003e: GFD responder rate 58%. Algera 2022 \u003cstrong\u003e[9]\u003c/strong\u003e: True responder rate (response only to GFD): 30%.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 158px;\"\u003e\n \u003cp\u003eNordin 2022/2023/2024 \u003cstrong\u003e[2,4,5]\u003c/strong\u003e: Gluten challenge showed no significant difference from placebo at group level.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eHigh efficacy heterogeneity; benefit likely limited to NCGS subset; efficacy in unselected IBS likely confounded by incidental FODMAP reduction.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2. Efficacy outcomes of dietary interventions for patients with irritable bowel syndrome (IBS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e LFD = low FODMAP diet; MD = Mediterranean diet; MED-LFD = Mediterranean low FODMAP diet; TDA = traditional dietary advice; SSRD = starch-sucrose-reduced diet; GFD = gluten-free diet; IBS-SSS = Irritable Bowel Syndrome Symptom Severity Score; ITT = intention-to-treat; CI = confidence interval; RCT = randomized controlled trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNotes:\u003c/strong\u003e Clinical response rate is defined as the percentage of patients achieving a reduction of \u0026ge;50 points in the IBS-SSS, unless otherwise specified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Risk of Bias Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRisk of bias for all included randomized controlled trials (RCTs) was assessed using the Cochrane RoB 2.0 tool for randomized trials, which evaluates six core domains:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(1) random sequence generation\u003c/p\u003e\n\u003cp\u003e(2) allocation concealment,\u003c/p\u003e\n\u003cp\u003e(3) blinding of participants and personnel\u003c/p\u003e\n\u003cp\u003e(4) blinding of outcome assessors\u003c/p\u003e\n\u003cp\u003e(5) incomplete outcome data\u003c/p\u003e\n\u003cp\u003e(6) selective reporting.\u003c/p\u003e\n\u003cp\u003eAn additional domain of \u0026quot;other bias\u0026quot; (e.g., baseline imbalance, small sample size, conflict of interest) was also considered.\u003c/p\u003e\n\u003cp\u003eDetailed domain-specific ratings for each study are summarized in Table 3, and a visual summary of overall risk of bias is presented in Figure 2\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3.1 Domain-specific Risk of Bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRandom sequence generation: 10 studies were rated as low risk (e.g., computer-generated randomization, random number tables), while 0 studies were rated as unclear risk due to insufficient reporting of sequence generation methods. No studies were rated as high risk in this domain.\u003c/p\u003e\n\u003cp\u003eAllocation concealment: 4 studies were rated as low risk (e.g., central randomization, sealed opaque envelopes), and 6 studies were rated as unclear risk (no description of concealment methods). No high-risk studies were identified here.\u003c/p\u003e\n\u003cp\u003eBlinding of participants and personnel: Due to the nature of dietary interventions (impossible to blind participants/staff to assigned diets), all studies were rated as high risk of performance bias. 0 studies were rated as unclear risk (no mention of blinding or mitigation strategies). This was the primary domain with high risk of bias across all included trials.\u003c/p\u003e\n\u003cp\u003eBlinding of outcome assessors: 8 studies were rated as low risk (blinded assessors for subjective outcomes like IBS-SSS), while 2 studies were unclear risk (no reporting of assessor blinding). No high-risk studies were found here.\u003c/p\u003e\n\u003cp\u003eIncomplete outcome data: 10 studies were rated as low risk (low loss-to-follow-up \u0026lt;10%, intention-to-treat analysis), and 0 studies were unclear risk (no reporting of missing data handling). No high-risk studies were identified.\u003c/p\u003e\n\u003cp\u003eSelective reporting: 10 studies were rated as low risk (registered in clinical trial databases, all pre-specified outcomes reported), while 0 studies were unclear risk (no trial registration or incomplete outcome reporting). No high-risk studies were found.\u003c/p\u003e\n\u003cp\u003eOther bias: 8 studies were rated as low risk (no baseline imbalance, adequate sample size), while 2 studies were unclear risk (small sample size \u0026lt;50 per arm, potential baseline imbalance). No high-risk studies were identified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3.2 Overall Risk of Bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall, the included RCTs were rated as having moderate overall risk of bias. The main limitation was high risk of performance bias (due to unavoidable lack of blinding in dietary interventions), while all other domains were predominantly low or unclear risk. No study was rated as high risk in more than one domain, suggesting the meta-analytic results are generally reliable, though subjective symptom outcomes may be slightly influenced by performance bias.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eStudy Design Type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eStudy (First author, Year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eBPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eBOA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eIOD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eSR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eOB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eOverall risk of bias\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eParallel RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eZhang Y, 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eParallel RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eRej A, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eCrossover RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eAlgera JP, 2022 (GFD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eCrossover RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eAlgera JP, 2022 (Low FODMAP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eParallel RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eNilholm C, 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eNon-inferior RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eRoth B, 2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eParallel RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eKasti AN 2025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003ePilot RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eSingh P, 2025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eUnclear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eParallel RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eBamidele JO, 2025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003eParallel RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003eNilholm C, 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3. Risk of bias assessment of the 10 included randomized controlled trials using the Cochrane Risk of Bias 2.0 tool.\u003c/p\u003e\n\u003cp\u003eAbbreviations: RS, random sequence generation; AC, allocation concealment; BPP, blinding of participants and personnel; BOA, blinding of outcome assessment; IOD, incomplete outcome data; SR, selective reporting; OB, other bias; Low, low risk of bias; Unclear, unclear risk of bias.\u003c/p\u003e\n\u003cp\u003eNotes: Blinding of participants and personnel was rated as high risk for all studies due to the inherent impossibility of blinding dietary interventions in real-world feeding or guidance trials. Therefore, the \u0026quot;Overall risk of bias\u0026quot; for all included trials is classified as \u0026quot;Moderate\u0026quot; (Some concerns).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4 Network Meta-analysis of Clinical Efficacy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4.1 Network Geometry\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA connected network was successfully constructed comprising 7 distinct nodes: LFD, MD, MED-LFD, TDA, SSRD, GFD, and Habitual/Control. The network incorporated 10 RCTs encompassing 939 participants. LFD and TDA served as the primary hub nodes, forming a robust closed-loop network geometry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4.2 Relative Efficacy of Dietary Interventions (League Table)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe league table of the network meta-analysis provided pairwise comparisons across all interventions. Compared with the Habitual/Control diet, all structured interventions demonstrated statistically significant superiority in achieving clinical response. Converting the network estimates to standard Risk Ratios (RR, Treatment vs. Control), MED-LFD exhibited the most robust treatment effect (RR = 2.37, 95% CI: 1.38\u0026ndash;4.07), followed by SSRD (RR = 2.25, 95% CI: 1.52\u0026ndash;3.34), MD (RR = 2.25, 95% CI: 1.35\u0026ndash;3.75), LFD (RR = 2.17, 95% CI: 1.45\u0026ndash;3.25), and GFD (RR = 2.10, 95% CI: 1.26\u0026ndash;3.50). TDA showed relatively lower efficacy (RR = 1.67, 95% CI: 1.04\u0026ndash;2.68).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 38px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eGFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eLFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eMED-LFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eSSRD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eTDA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 38px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.83 (0.30, 2.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.60 (0.25, 1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.36 (0.22, 0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 38px;\"\u003e\n \u003cp\u003eGFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.48 (0.29, 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eGFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.06 (0.69, 1.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.36 (0.83, 2.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 38px;\"\u003e\n \u003cp\u003eLFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.46 (0.31, 0.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.97 (0.67, 1.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eLFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.13 (0.71, 1.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.99 (0.84, 1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.20 (0.89, 1.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 38px;\"\u003e\n \u003cp\u003eMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.44 (0.27, 0.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.94 (0.59, 1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.96 (0.70, 1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.46 (1.05, 2.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 38px;\"\u003e\n \u003cp\u003eMED-LFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.42 (0.25, 0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.89 (0.55, 1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.92 (0.63, 1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.95 (0.65, 1.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eMED-LFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.42 (1.09, 1.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 38px;\"\u003e\n \u003cp\u003eSSRD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.44 (0.30, 0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.93 (0.63, 1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.96 (0.82, 1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.00 (0.70, 1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.05 (0.70, 1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eSSRD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 38px;\"\u003e\n \u003cp\u003eTDA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e0.60 (0.37, 0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.26 (0.85, 1.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.30 (1.00, 1.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.35 (1.02, 1.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.42 (1.09, 1.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003e1.35 (0.99, 1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 77px;\"\u003e\n \u003cp\u003eTDA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable4.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eLeague Table\u003c/p\u003e\n\u003cp\u003eData are presented as Risk Ratios (RRs) with 95% Confidence Intervals. The lower-left triangle indicates pooled NMA estimates (random-effects model); the upper-right triangle indicates direct pairwise evidence. An RR \u0026gt; 1 favors the intervention in the row compared to the column. MED-LFD ranked first with a P-score of 0.76.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4.3 Treatment Ranking (P-scores)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to the P-score ranking matrix, which evaluates the probability of each diet being the best intervention for achieving clinical response, the hierarchy of efficacy was established as follows:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eMED-LFD (P-score = 0.7592)\u003c/li\u003e\n \u003cli\u003eSSRD (P-score = 0.6970)\u003c/li\u003e\n \u003cli\u003eMD (P-score = 0.6795)\u003c/li\u003e\n \u003cli\u003eLFD (P-score = 0.6001)\u003c/li\u003e\n \u003cli\u003eGFD (P-score = 0.5634)\u003c/li\u003e\n \u003cli\u003eTDA (P-score = 0.1973)\u003c/li\u003e\n \u003cli\u003eHabitual/Control (P-score = 0.0036)\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003e3.4.4 Heterogeneity and Inconsistency Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe robustness of the network model was highly satisfactory. The global inconsistency test showed no significant disparity between the direct and indirect network designs. Crucially, the node-splitting method confirmed local consistency across all closed loops, with all P-values well above the significance threshold (ranging from 0.137 to 0.623), indicating robust agreement between direct and indirect evidence. Furthermore, the comparison-adjusted funnel plot demonstrated a highly symmetric distribution, suggesting an absence of significant publication bias or small-study effects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 Acceptability and Safety\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5.1 Acceptability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTraditional dietary advice (TDA) demonstrated superior acceptability across patient-reported measures. Rej A (2022) reported that TDA was perceived as significantly cheaper (49% of TDA patients reported increased cost vs 82% for GFD and LFD; P\u0026lt;0.01), less time-consuming for grocery shopping (39% of TDA patients reported extra time vs 79% for LFD and 70% for GFD; P\u0026lt;0.01), and easier to follow when eating out (52% of TDA patients reported difficulty vs 67% for LFD and GFD; P=0.03) [9]. TDA was also easier to incorporate into daily life than LFD (55% of TDA patients reported easy incorporation vs 33% for LFD; P=0.02) [8].\u003c/p\u003e\n\u003cp\u003eThe Mediterranean diet (including combined MED-LFD) showed favorable acceptability. Kasti AN (2025) reported a 75% adherence rate (\u0026quot;most of the time\u0026quot; or \u0026quot;every day\u0026quot;) and 96.3% follow-up completion rate at first follow-up [7]. A pure Mediterranean diet pilot study reported 93.8% compliance based on 3-day food diaries [6].\u003c/p\u003e\n\u003cp\u003eLFD showed moderate acceptability. Roth B (2024) reported good short-term adherence (78.2% response rate at 4 weeks), but only 36.7% of patients continued a personalized LFD at 6-month follow-up [11]. Patients reported challenges with strict FODMAP calculation and increased shopping time [9,11]. A feeding trial with provided meals reported 94% compliance, reflecting an idealized rather than real-world setting [8].\u003c/p\u003e\n\u003cp\u003eSSRD demonstrated higher patient preference and long-term adherence compared with LFD. Among patients who tested both diets, 64.7% (22/34) preferred SSRD, citing ease of adherence (16 patients) or combined ease and efficacy (7 patients) [11]. At 6-month follow-up, 52.8% of SSRD patients continued a modified diet vs 36.7% of LFD patients (P=0.005), supporting better long-term acceptability [11].\u003c/p\u003e\n\u003cp\u003eDropout rates across all studies ranged from 3.7% to 23.1%, with the lowest rates in TDA and MED-LFD groups (3.7%\u0026ndash;9.5%) [6,7,8] and higher rates in LFD and GFD groups (11.1%\u0026ndash;23.1%) [5,8,11].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5.2 Safety\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll four dietary interventions were safe and well-tolerated, with no serious adverse events (SAEs) reported in any included study [1-11]. Mild adverse events were predominantly transient, self-limiting gastrointestinal symptoms related to dietary adaptation.\u003c/p\u003e\n\u003cp\u003eLFD: Transient bloating was reported during initial adaptation [8]. One case of constipation led to study withdrawal in the strict LFD subgroup (4 g/day) [6]; all other mild events resolved spontaneously.\u003c/p\u003e\n\u003cp\u003eMediterranean diet (including MED-LFD): Occasional mild bloating was observed, with 8 non-specific adverse events (headache, fatigue, mild abdominal worsening) equally distributed across treatment arms [7]. No patients withdrew due to adverse events in the MED-LFD group [7]; one patient in the pure Mediterranean diet pilot withdrew due to worsening abdominal pain [6].\u003c/p\u003e\n\u003cp\u003eTDA: The lowest incidence of mild adverse events was reported, with minimal transient gastrointestinal symptoms that resolved rapidly [6,9].\u003c/p\u003e\n\u003cp\u003eSSRD: No adverse events related to dietary restriction were reported during long-term follow-up [11]; any initial transient digestive symptoms were mild and self-limiting [6].\u003c/p\u003e\n\u003cp\u003eWith the exception of two withdrawals in the Singh P (2025) pilot study (one LFD-related constipation, one Mediterranean diet-related abdominal pain), no patients withdrew from studies due to adverse events [6].\u003c/p\u003e\n\u003cp\u003eA concise comparison of acceptability, adherence, dropout rates, and safety profiles of the four main dietary interventions is provided in Table 4.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eDiet type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eAcceptability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eAdherence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eDropout rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eSafety\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eLow FODMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e78%\u0026ndash;95%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e19%\u0026ndash;23.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eBloating reported (occasional);\u003c/p\u003e\n \u003cp\u003eone case of constipation leading to withdrawal [8]; onset during adaptation period (1-2 weeks), spontaneous resolution\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eMediterranean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e75% (Kasti 2025) [7]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e3.7%\u0026ndash;5.8% [7,8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eEight AEs reported (headache, fatigue, abdominal symptoms) [7]; one withdrawal due to abdominal pain (pure MD) [8]; all transient\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eTraditional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eHighest\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026gt;95% (inferred)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e5.8%\u0026ndash;9.5% [6,9]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eMinimal reports of transient gastrointestinal symptoms; rapid spontaneous resolution\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eEmerging (SSRD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026gt;90% (inferred)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026lt;10% (short-term) [6,11]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003eOccasional bloating reported; transient and self-limiting; no AEs during long-term follow-up [11]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 4. Acceptability and safety outcomes of dietary interventions for patients with irritable bowel syndrome (IBS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e IBS = irritable bowel syndrome; SSRD = starch-sucrose-reduced diet; AEs = adverse events; MD = Mediterranean diet.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNotes:\u003c/strong\u003e Adherence and dropout rates are presented as ranges across included studies or single-study values where only one study reported the outcome. Acceptability ratings (Moderate/High/Highest) are based on subjective patient-reported outcomes from the included trials. All reported adverse events were mild and transient; no serious adverse events (SAEs) were documented in any study [1-11].\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e\u003cstrong\u003e4.1 Key Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present systematic review and meta-analysis included 10 randomized controlled trials (RCTs) enrolling 939 adult patients with irritable bowel syndrome (IBS), comprehensively evaluating the efficacy, acceptability, and safety of four dietary interventions: the low FODMAP diet (LFD), Mediterranean diet (including pure MD and Mediterranean-low FODMAP hybrid diet [MED-LFD]), traditional dietary advice (TDA), and Emerging diet (SSRD, GFD). The core findings are summarized as follows:\u003c/p\u003e\n\u003cp\u003e1. Efficacy Outcomes and Hierarchy of Dietary Interventions\u003c/p\u003e\n\u003cp\u003eA major contribution of this study is the establishment of a clear efficacy hierarchy among IBS dietary interventions through network meta-analysis (NMA), overcoming the limitations of previous traditional pairwise meta-analyses that often clumped distinct control diets into ambiguous categories.\u003c/p\u003e\n\u003cp\u003eOur NMA definitively ranked the hybrid MED-LFD as the most effective intervention (P-score = 0.76). This indicates that combining the anti-inflammatory benefits of a Mediterranean pattern with the osmotic and fermentative reduction of LFD yields synergistic therapeutic effects, offering excellent and sustained symptom control.\u003c/p\u003e\n\u003cp\u003eNotably, SSRD emerged as the second highest-ranking diet (P-score = 0.70), outperforming the classical LFD (P-score = 0.60). This robust statistical evidence confirms that targeting sucrase-isomaltase pathways through starch and sucrose reduction is a highly viable, non-inferior alternative to FODMAP restriction, particularly given its superior patient preference and long-term adherence reported in descriptive analyses.\u003c/p\u003e\n\u003cp\u003eWhile TDA demonstrated statistical superiority over habitual diets, it consistently ranked near the bottom among structured therapies (P-score = 0.20), suggesting that unstructured advice, despite its ease of implementation, should ideally serve as a baseline or adjunctive strategy rather than a definitive standalone treatment for moderate-to-severe IBS.\u003c/p\u003e\n\u003cp\u003e2. Acceptability and Safety\u003c/p\u003e\n\u003cp\u003eAll interventions were generally safe, with no serious adverse events reported; mild adverse events (e.g., transient bloating, flatulence) were self-limiting. TDA had the highest acceptability, attributed to lower financial cost and reduced time burden for patients, alongside the lowest dropout rates (3.7%\u0026ndash;9.5%), comparable to MED-LFD. SSRD demonstrated better long-term adherence and patient preference compared with LFD, likely due to less restrictive dietary rules, while LFD showed acceptable short-term adherence but higher dropout rates in long-term follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.2 Mechanistic Rationale and Interpretation of Heterogeneity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMechanistic challenge studies provide the critical pathophysiological rationale for dietary interventions and help interpret the heterogeneity observed in therapeutic trials.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA series of double-blind, placebo-controlled crossover studies by Nordin et al. confirmed that FODMAPs, but not gluten, are specific triggers of IBS symptoms at the group level [2,4,5]. In their 2022 study, high-dose FODMAP intervention (50 g/day) significantly exacerbated IBS-SSS scores compared with placebo (mean 240 vs. 198; P=0.00056), while gluten challenge (17.3 g/day) showed no significant difference from placebo [2]. These findings validate the therapeutic rationale for FODMAP restriction, explaining why LFD yields consistent clinical efficacy across diverse study settings (low heterogeneity, I\u0026sup2;=0%).\u003c/p\u003e\n\u003cp\u003eConversely, the high heterogeneity observed in GFD trials and the variable efficacy of GFD in clinical trials can be mechanistically explained by these data. The lack of a consistent symptomatic response to isolated gluten challenge suggests that symptom improvement in some GFD trials may be attributable to the concurrent reduction of FODMAPs (e.g., fructans in wheat) rather than gluten removal per se [3,9]. Therefore, GFD is not universally effective for the general IBS population; its benefit is likely confined to a small subset of patients with underlying gluten sensitivity, for whom reliable predictors remain to be established.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.3 Comparison with Previous Studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings align with prior systematic reviews demonstrating that LFD is a consistent, well-tolerated dietary intervention for IBS, but not superior to other evidence-based dietary strategies. The inferior efficacy of TDA observed in our analysis is consistent with clinical consensus that unstructured, general dietary advice yields weaker outcomes compared with structured, mechanism-targeted diets (e.g., LFD, SSRD).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNotably, our study extends previous findings by evaluating the crucial balance between short-term efficacy and long-term nutritional safety. Previous systematic reviews, such as Wang et al. (2021) [12], have highlighted that while traditional LFD provides rapid symptom relief, its long-term strict implementation raises concerns regarding nutritional inadequacy and significant reductions in beneficial gut microbiota (e.g., \u003cem\u003eBifidobacteria\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eIn contrast, our network analysis underscores the superiority of the hybrid MED-LFD approach, aligning with the recent groundbreaking findings by Kasti et al. (2025) [7]. By embedding low-FODMAP principles within a Mediterranean dietary pattern, the MED-LFD not only mitigates the nutritional limitations of traditional LFD but also harnesses the anti-inflammatory and microbiome-modulating properties of Mediterranean polyphenols and omega-3 fatty acids. This synergy likely explains its top-ranking efficacy and profound improvements in IBS-related quality of life (IBS-QoL) and psychological well-being. For emerging interventions, the non-inferiority of SSRD to LFD supports its potential as a more sustainable alternative, whereas the high heterogeneity in GFD trials suggests its benefits are likely confined to non-celiac gluten sensitivity subgroups rather than the general IBS population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.4 Clinical Implications: A Stepped Dietary Therapy Framework\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on our network meta-analysis, combined with acceptability and mechanistic evidence, we propose a stepped, personalized dietary therapy framework for IBS management:\u003c/p\u003e\n\u003cp\u003eFirst-line therapy (Low burden \u0026amp; High acceptability): TDA.\u003c/p\u003e\n\u003cp\u003eAs highlighted by Rej et al. [8], while highly structured diets like LFD and GFD show robust clinical efficacy, TDA significantly outperforms them in patient acceptability, cost-effectiveness, and ease of real-world implementation. Therefore, TDA should serve as the universal first-line strategy, particularly for patients prioritizing maximum dietary flexibility and minimal financial burden.\u003c/p\u003e\n\u003cp\u003eSecond-line therapy (Targeted \u0026amp; Structured): LFD or SSRD.\u003c/p\u003e\n\u003cp\u003eFor patients unresponsive to TDA, structured diets targeting specific pathophysiological mechanisms should be implemented. LFD remains the gold standard for targeting osmotic load and fermentation. Notably, SSRD emerges as a highly viable, non-inferior alternative (targeting sucrase-isomaltase insufficiency) with higher patient preference and long-term adherence, making it an excellent option for those who struggle with the complexity of FODMAP restriction.\u003c/p\u003e\n\u003cp\u003eLong-term maintenance: MED-LFD.\u003c/p\u003e\n\u003cp\u003eGiven the long-term nutritional risks associated with strict elimination diets, integrating Mediterranean principles (MED-LFD) is highly recommended for maintenance. This hybrid approach ensures sustained symptom control while providing cardiovascular and neuro-protective benefits, making it the optimal long-term strategy for chronic IBS management.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4.5 Limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Limited Head-to-Head Comparisons for Emerging Diets: While SSRD and GFD showed promising results in our network model, the number of direct head-to-head trials remains small, resulting in wider 95% confidence intervals for some comparisons.\u003c/p\u003e\n\u003cp\u003e2. Performance Bias and Open-Label Nature: Due to the inherent nature of dietary interventions, blinding of participants and personnel was not feasible across the 10 included RCTs. This may influence patient-reported subjective outcomes, such as IBS-SSS scores and quality-of-life assessments.\u003c/p\u003e\n\u003cp\u003e3. Heterogeneity in GFD Responders: The clinical efficacy of GFD exhibited significant variability between studies, likely reflecting the confounding effect of incidental FODMAP (fructan) reduction when removing wheat, rather than a specific gluten-related response.\u003c/p\u003e\n\u003cp\u003e4. Geographic and Cultural Bias: Most studies were conducted in Western or Mediterranean contexts (Sweden, USA, UK, Greece, China). The applicability of these dietary frameworks to other cultural dietary patterns (e.g., African or Southeast Asian contexts) requires further validation.\u003c/p\u003e\n\u003cp\u003e5. Long-term Sustainability Data: Although some recent trials (e.g., Kasti et al., 2025; Roth et al., 2024) provided 6-month follow-up data, evidence regarding the sustainability and impacts on gut microbiota beyond 12 months is still lacking for most interventions.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eDietary management of IBS should transition from a \u0026quot;one-size-fits-all\u0026quot; approach to a personalized, stepped strategy. Our network meta-analysis demonstrates that while structured diets effectively relieve symptoms, they possess distinct clinical profiles. Traditional dietary advice (TDA) should be the first-line intervention due to its superior patient acceptability, lower cost, and ease of implementation. For TDA non-responders, targeted structured diets like SSRD or LFD should be initiated, with SSRD offering non-inferior efficacy and better adherence than LFD. Crucially, for long-term maintenance, the hybrid Mediterranean-low FODMAP diet (MED-LFD) ranks as the most effective overall strategy, uniquely balancing sustained symptom control with long-term nutritional safety and quality of life improvements.\u003c/p\u003e\n\u003cp\u003eClinical decisions should integrate symptom severity, bowel habits, patient preference, adherence capacity, economic status, and access to dietary guidance. Future research requires head-to-head RCTs, particularly for MD, and long-term follow-up.\u003c/p\u003e\n\u003cp\u003eFuture research should prioritize:\u003c/p\u003e\n\u003cp\u003e(1) \u003cstrong\u003eHead-to-head RCTs\u003c/strong\u003e directly comparing all four dietary interventions in the same population, particularly for MD where direct comparisons with LFD remain limited [13];\u003c/p\u003e\n\u003cp\u003e(2) \u003cstrong\u003eSubtype-stratified research\u003c/strong\u003e to establish IBS subtype-specific dietary strategies, as IBS-D patients may derive greater benefit from LFD for bowel habit improvement [2,10];\u003c/p\u003e\n\u003cp\u003e(3) \u003cstrong\u003eProtocol standardization\u003c/strong\u003e (e.g., strict vs. moderate LFD criteria, standardized TDA definition) to reduce inter-study heterogeneity;\u003c/p\u003e\n\u003cp\u003e(4) \u003cstrong\u003eLong-term follow-up\u003c/strong\u003e (\u0026ge;12 months) to evaluate sustainability and impacts on gut microbiota and nutritional status;\u003c/p\u003e\n\u003cp\u003e(5) \u003cstrong\u003ePopulation diversification\u003c/strong\u003e to include non-Western ethnic groups, improving generalizability and exploring combined or sequential dietary approaches for non-responders\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDeclaration of AI Assistance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript was written by the authors and edited with the assistance of artificial intelligence (AI) for language polishing purposes only. The authors take full responsibility for the content, originality, and integrity of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Reporting Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll reported percentages and means are presented with 95% confidence intervals where calculable from the original publications. Between-group comparisons are accompanied by P-values as reported in the original studies. In cases where original studies did not provide confidence intervals or P-values for specific comparisons, this is noted in the text. The qualitative descriptors (e.g., \u0026quot;high,\u0026quot; \u0026quot;moderate\u0026quot;) used in the acceptability section are derived from patient-reported outcome measures from the included trials, as detailed in Section 3.3.1, and do not represent statistical judgments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis systematic review is based on published and publicly available data from the included randomized controlled trials. No new original data were generated or analyzed in this study. All data supporting the results of this review are available from the corresponding author upon reasonable request.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eX.Y. conceptualized and designed the study, conducted the systematic literature search and data extraction, performed the frequentist network meta-analysis and statistical analyses, drafted the original manuscript, and prepared all figures and tables. X.Y. critically revised the manuscript for important intellectual content and approved the final version for submission.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhang Y, Feng L, Wang X, et al. 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BMJ (Clin Res Ed) 343:d5928. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/bmj.d5928\u003c/span\u003e\u003cspan address=\"10.1136/bmj.d5928\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\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":"Irritable bowel syndrome, Dietary intervention, Low FODMAP diet, Mediterranean diet, Traditional dietary advice, Starch and sucrose-reduced diet, Gluten-free diet, Systematic review, Meta-analysis","lastPublishedDoi":"10.21203/rs.3.rs-9245067/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9245067/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDietary interventions are first-line management for irritable bowel syndrome (IBS), but their relative efficacy, acceptability, and safety remain incompletely understood. This systematic review and meta-analysis aimed to comprehensively evaluate five dietary interventions (LFD, MD/MED-LFD, TDA, SSRD, GFD) for adult IBS patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe searched PubMed, Embase, Cochrane Library, and Web of Science for RCTs published between 2019 and 2025 comparing dietary interventions for IBS. Meta-analyses were performed using a random-effects model, and risk of bias was assessed using the Cochrane RoB 2.0 tool.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTen RCTs involving 939 participants were included. Frequentist network meta-analysis demonstrated that all specific dietary interventions were significantly superior to habitual diet/control. Based on the P-score ranking matrix, the combined Mediterranean-low FODMAP diet (MED-LFD) had the highest probability of being the most effective intervention (P-score\u0026thinsp;=\u0026thinsp;0.76), followed by the starch- and sucrose-reduced diet (SSRD, P-score\u0026thinsp;=\u0026thinsp;0.70), Mediterranean diet alone (MD, P-score\u0026thinsp;=\u0026thinsp;0.68), and LFD (P-score\u0026thinsp;=\u0026thinsp;0.60). Traditional dietary advice (TDA) showed lower comparative efficacy (P-score\u0026thinsp;=\u0026thinsp;0.20). Node-splitting analysis confirmed the robustness of the network model with no significant local inconsistency (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05 for all).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLFD, MED-LFD, TDA, SSRD, and GFD have distinct efficacy, acceptability, and safety profiles. LFD is a reliable first-line option, MED-LFD offers favorable long-term outcomes, TDA is acceptable but less effective, SSRD is a viable alternative to LFD, and GFD is only suitable for specific subgroups. Further research is needed to confirm long-term efficacy and identify subgroup responders.\u003c/p\u003e","manuscriptTitle":"Characteristics and clinical applicability of five dietary interventions for irritable bowel syndrome: a Systematic review and Network meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 06:53:26","doi":"10.21203/rs.3.rs-9245067/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":"41e686dc-17b3-4941-9623-1887784e467e","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-14T07:39:57+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 06:53:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9245067","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9245067","identity":"rs-9245067","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}