Gut microbiota composition and functional classification in preschool children with allergic rhinitis and functional constipation

Gut microbiota composition and functional classification in preschool children with allergic rhinitis and functional constipation | 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 Article Gut microbiota composition and functional classification in preschool children with allergic rhinitis and functional constipation Zhenyu Yang, Chunyan Wang, Weikeng Yang, Dongming Meng, Wei Kong, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4493967/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 Objective Studies suggest that functional constipation (FC) is more common in preschool children with allergic rhinitis (AR) compared to those without. FC can significantly impact a child's quality of life. This study investigated the relationship between AR and FC in children diagnosed with both conditions (disease group) and a healthy control group. We compared the gut microbiota (GM) composition of children in both groups. Methods The 16S rRNA sequencing technology was employed to compare the GMsequencing results of 32 children with AR and FC and 21 healthy children. Results Compared with the healthy group: 1) the GM α-diversity in the disease group was significantly higher ( P =0.014); 2) At the phylum level, the abundance of Bacteroidetes (P<0.05) decreased significantly, while that of Proteobateria was increased significantly in the disease group (P<0.05); 3) At the genus (species) level, the abundance of Bifidobacterium , Phascolarctobacterium , Veillonella ( Veillonella_parvula , Veillonella_dispar ), Escherichia/Shigella , Klebsiella ( Klebsiella_pneumoniae ) ,Streptococcus, Escherichia/Shigella and Bacteroides_thetaiotaomicron increased (P<0.05), but the abundance of Bacteroides ( Bacteroides_uniformis ) , Faecalibacterium ( Faecalibacterium_prausnitzii ) , Ruminococcus, Kineothrix ( Kineothrix_alysoides ) , Anaerostipes ( Anaerostipes_hadrus ) and Bifidobacterium_longum decreased significantly in disease group (P<0.05). 4) The abundance of functional pathways related to carbohydrate metabolism, lipid metabolism, Transport_and_Catabolism, Endocrine_System, Nervous_System, Metabolic_Diseases and Immune_System were significantly decreased. 5) Furthermore, GM was found to be correlated with the clinical features of the disease group. Conclusion Analysis of the GM composition and function in the disease group suggests that supplementing the disease group with probiotics that produce butyric acid and dietary fiber (prebiotics) may correct dysregulation of GM, thereby improve AR and FC symptoms. Biological sciences/Microbiology Health sciences/Medical research Preschool age Allergic rhinitis Functional constipation Gut microbiota Microbiota Function Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Allergic rhinitis (AR) is a chronic inflammatory allergic disease affecting the nasal mucosa associated with Th1/Th2 imbalance following exposure to allergens. The secretion of cytokines such as IL-4 and IT-5 induced by Th2 cells, followed by the production of IgE leads to the emergence of chronic inflammation of nasal mucosa, manifesting as a runny nose, nasal congestion, sneezing, nasal itching and other symptoms. Currently, AR affects 40% of the global population, and the incidence of allergic diseases in children in China has been increasing in the past 20 year[ 1 ]. The most recent study found that the prevalence of AR in children in China has exceeded 20%, AR is associated with the development of several conditions, including upper airway cough syndrome, sinusitis, middle ear infections, adenoid hypertrophy, cough variant asthma, and gastroesophageal reflux [ 2 ]. Moreover, a considerable proportion of children with AR experience gastrointestinal symptoms, such as anorexia, poor appetite, FC, diarrhea, weight loss, anemia, and low vitamin D levels [ 3 ]. Studies have demonstrated that FC is often caused by a lack of dietary fiber, GM dysbiosis, among other factors [ 4 – 7 ]. FC can cause anal fissures, rectal bleeding, impaction, painful defecation, tense defecation, and other phenomena, all which seriously affect the quality of life of AR children [8; 9], and FC can potentially increase the risk of AR [ 7 ]. Modern medicine has demonstrated that patients with respiratory system diseases often experience gastrointestinal diseases such as inflammatory bowel disease, and about 50% of inflammatory bowel disease patients manifest varying degrees of lung function damage, leading to the concept of the "gut-lung axis"[ 10 ]. Embryology research have revealed that the human lung and trachea are derived from the foregut of the primitive gut, and differentiate into respiratory epithelium and glands, suggesting that the structures of the gastrointestinal tract and respiratory tract share the same origin [ 11 ]. Respiratory diseases and antibiotic use can significantly alter the GM, affecting its diversity and composition. Conversely, various intestinal diseases, like ulcerative colitis, can sometimes cause respiratory symptoms and alterations in the microbes that reside in the lungs. Interestingly, research suggests that probiotics may be beneficial in alleviating respiratory allergic diseases[ 12 ]. Although several studies have explored the relationship between AR and GM in adults, only two reports have reported this relationship in children. Chiu et al. [ 13 ] investigated AR children aged 4.4–6.8 years found that the abundance of Firmicutes was decreased at the phylum level, and the abundance of genera such as Dialister and Dorea was also reduced. Hu et al. [ 14 ] explored AR children with functional gastrointestinal disorders under the age of 3 and uncovered that these children had abnormal GM and abnormal intestinal endocrine hormones, and the two were correlated. While the link between GM and various health conditions has been explored extensively, there's a lack of research on GM in preschool children with AR who also experience FC. Our clinical observations suggested a higher prevalence of FC in preschoolers with AR. To investigate this further, we compared the gut microbiota composition and function between two groups of children: preschoolers with AR and FC, and healthy children of the same age. 2. Materials and Methods 2.1 Patients Patients who met the diagnostic criteria for AR in the "Chinese guideline for diagnosis and treatment of allergic rhinitis (2022, revision)" [ 2 ] and the diagnostic criteria for FC in the New Roman IV system [ 15 ] were included in this study. Next, 32 AR and FC preschool children who were treated at Longgang District Maternity&Child Healthcare Hospital in Shenzhen from January 2022 to December 2023 were assigned to the disease group, and data of 21 healthy children of the same age (healthy group) obtained from published literature were used for comparison. We excluded children with the following conditions: severe liver disease, dysplasia, severe infections, and any antibiotic or microbial medication use within the month prior to sample collection. This study was approved by the ethics committee of Longgang District Maternity & Child Healthcare Hospital of Shenzhen city with the registration number of LGFYKYXMMLL-2023-1. The parents, as legal guardians, voluntarily accepted scientific research on their children's care, informed consent was obtained from the parents and their legal guardians.Our Research have been performed in accordance with the Declaration of Helsinki. 2.2 Sampling, sequencing and bioinformatics 5 g central of midcourse feces were collected and frozen at -80℃ immediately. Total DNA was extracted using PowerSoil® DNA Isolation Kit (MoBio, USA) and amplified by 16S rDNA V3-V4 regions primers for next-generation sequencing (Illumina, USA). Raw sequencing data were subjected to quality control and assembled to tags using FLASH (v1.2.11), and were clustered to operational taxonomic units (OTUs). To classify the gut microbiota (GM), we used a reference database called Greengene (version 201305). This database helps us assign taxonomic labels (like genus and phylum) to the different microbes identified in the samples. In addition to classification, we also analyzed the predicted functions of the GM using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Finally, we compared variations in microbial communities (at the genus and phylum levels) between the different groups involved in the study. 2.3 Statistic analysis The principle components analysis (PCA) was conducted using the ade4 package (v1.7-22) in R software (v3.3.3). Differences between different groups or subgroups were compared using the Wilcoxon sum-rank test at the taxonomic levels of genus and phylum, and at GM function. Correlation analysis was performed by Spearman coefficient between genus and clinical syndromes. 3. Results 3.1 The GM diversity was significantly increased in the disease group Differences in GM diversity and composition between disease group and healthy children were analyzed and the results were as follows: 1) the GM α-diversity in disease group was significantly higher than that in healthy group (2.257 ± 0.367 vs 1.980 ± 0.352, P = 0.014, Fig. 1 ); 2) PCA dimension reduction analysis showed that the GM composition in half of the disease group was similar to that in healthy children, but that of another disease group was different from that of healthy children. The main diverse genera were Prevotella, Bacteroides , Agathobacter, Parasutterella, Phocaeicola among others (Fig. 2 ). 3.2 The phyla were different between disease group and healthy group The top 5 phyla, which accounted for 99.45% and 99.80% proportion of GM in the disease group and healthy children, respectively, were selected. Compared to disease group, Bacteroidetes was significantly higher in the healthy group (p = 0.045, Table 1 ), but Proteobacteria was decreased in healthy group (p = 0, Table 1 ). The differences of abundance of the remaining phyla were not significant (p > 0.05, Fig. 3 , Table 1 ). Table 1 Analysis of phyla in children from the disease and control groups (top 5) Top 5 phyla Disease group Control group P-value FDR Mean (%) SD (%) Mean (%) SD (%) Bacteroidetes 40.06 19.22 50.72 12.21 0.049 0.138 Firmicutes 46.47 17.41 43.38 13.25 0.709 0.709 Proteobacteria 7.92 9.26 1.94 1.33 0.001 0.005 Actinobacteria 4.39 6.32 3.38 8.85 0.057 0.138 Verrucomicrobia 0.85 1.99 0.38 1.02 0.214 0.321 3.3 The dominant genus in disease group was different from that in healthy group The top 11 bacterial genera were compared between the disease group and the healthy group, and the results that the abundance of the following microbiota was increased in the disease group: Bifidobacterium , Phascolarctobacterium , Veillonella , Escherichia/Shigella , Klebsiella,Streptococcus , among others. (P < 0.05). The genera with decreased abundance in disease group were Bacteroides, Faecalibacterium, Ruminococcus, Kineothrix, Anaerostipes . P < 0.05) (Fig. 3 , Table 2 ). Table 2 Comparison of the top 11 dominant genera in the two groups of children Top 11 dominant genus Disease group Control group P-value FDR Mean (%) SD(%) Mean (%) SD(%) Bacteroides 14.28 13.32 20.76 12.87 0.039 0.243 Faecalibacterium 10.5 9.5 14.84 8 0.039 0.243 Bifidobacterium 4.21 6.31 3.12 8.81 0.02 0.187 Ruminococcus 0.82 1.51 2.83 4.23 0.019 0.187 Phascolarctobacterium 1.79 2.88 0.25 0.5 0.045 0.262 Escherichia/Shigella 1.57 2.86 0.17 0.27 0.025 0.198 Veillonella 1.59 3.34 0.07 0.14 0 0.007 Klebsiella 1.13 3.03 0.13 0.43 0.035 0.243 Kineothrix 0.18 0.26 1.52 3.03 0.003 0.044 Anaerostipes 0.35 0.55 0.58 0.42 0.01 0.115 Streptococcus 0.38 0.56 0.12 0.21 0.002 0.041 3.4 The dominant species in disease group was different from that in healthy group The top 11 bacterial species were compared between the disease group and the healthy group, and the results showed a significant increase in abundance of the species in the disease group: Klebsiella_pneumoniae , Bacteroides_thetaiotaomicron , Veillonella_parvula , Veillonella_dispar, Flavonifractor_plautii (P < 0.05). The species that showed decreased abundance in disease group included: Faecalibacterium_prausnitzii, Bacteroides_uniformis, Kineothrix_alysoides, Bifidobacterium_longum , and Anaerostipes_hadrus . (P < 0.05) (Table 3 ). Table 3 Comparison of the top 11 dominant species in the two groups of children Top 11 dominant genus Disease group Control group P-value FDR Mean (%) SD(%) Mean (%) SD(%) Faecalibacterium_prausnitzii 10.5 9.5 14.84 8.0 0.039 0.276 Bacteroides_uniformis 2.85 5.53 6.7 5.63 0.004 0.063 Klebsiella_pneumoniae 1.13 3.03 0.13 0.43 0.035 0.276 Kineothrix_alysoides 0.18 0.26 1.52 3.03 0.003 0.054 Bifidobacterium_longum 0.02 0.12 1.23 4.03 0.000 0.000 Anaerostipes_hadrus 0.34 0.55 0.58 0.42 0.006 0.079 Bacteroides_thetaiotaomicron 0.66 1.06 0.06 0.07 0.002 0.008 Veillonella_parvula 0.54 1.49 0.003 0.007 0.000 0.000 Veillonella_dispar 0.43 0.85 0.02 0.03 0.004 0.063 Flavonifractor_plautii 0.32 0.33 0.15 0.18 0.013 0.155 Faecalibacterium_prausnitzii 10.5 9.5 14.84 8 0.039 0.276 3.5 There were differences in GM function between disease group and healthy group Differences in GM composition can alter the function of flora. Therefore, we analyzed differences in GM function between children in the disease group and the healthy group. Compared with the healthy children group, the abundance of functional genes related to genetic information processing and Xenobiotics_Biodegradation_and_Metabolism was significantly higher in the disease group (p < 0.05, Fig. 4 ). The abundance of functional pathway related to carbohydrate metabolism, lipid metabolism, Transport_and_Catabolism, Endocrine_System, Nervous_System, Metabolic_Diseases and Immune_System was significantly lower (p < 0.05, Fig. 4 ). 3.6 GM in children with AR is correlated with clinical phenotype To investigate whether GM changes can alter the development of clinical symptoms of AR, we analyzed the correlation between GM and the clinical phenotype of children in the disease group. It was observed that the genera that were negatively correlated with allergy sources such as house dust mite were Blautia, Fusicatenibacter , and Ruminococcus . The genus Phocaeicola was positively correlated with skin allergies such as eczema, while the genus Lachnospira was negatively correlated. The genus Haemophilus showed a positive relationship with FC, while Dysosmobacter and Flintibacter were negatively correlated. The genus that showed a negative associated with snoring was Prevotella . Moreover, Phocaeicola , Veillonella and Mediterraneibacter were negatively associated with nose picking and nose rubbing. The genus that showed a positive correlation with runny nose was Anaerotignum and that with a negative correlation with runny nose was Dorea . The genus that showed a positive correlation with nasal congestion was Haemophilus , while those with a negative correlation were Megamonas, Ruthenibacterium, Eisenbergiella, Coprococcus and Butyricimonas . Streptococcus was positively correlated with sneezing, while Megamonas and Akkermansia were negatively correlated. The genera that were negatively associated with recurrent cough were Lachnospiracea incertae sedis, Ligilactobacillus, Erysipelatoclostridium and Intestinibacter (Fig. 5 ). 4. Discussion Allergic rhinitis (AR) is a prevalent condition in children. It can trigger a cascade of bothersome symptoms, including frequent respiratory infections, chronic cough, functional constipation (FC), and other complications [ 2 ]. These issues can significantly impact a child's quality of life[8; 9]. AR is often treated with antihistamines, leukotriene receptor antagonists, and nasal corticosteroids, while FC is mainly treated with laxatives such as lactulose and glycerin. However, recent studies have indicated that AR, FC, and dysbiosis of GM are closely related[13; 14]. Elsewhere, supplementation of probiotics and prebiotics based on GM was found to improve symptoms of AR and FC [ 16 – 18 ]. However, there is no consensus on how to select appropriate types of probiotics and prebiotics for these children [19; 20]. 4.1 Dysfunction of GM leading to chronic inflammation, inducing or exacerbating AR and FC In this study, the disease group experienced the GM disorder, whereas the abundance of Bacteroidetes in the phyla was significantly reduced, while that of Proteobacteria was significantly increased, which is inconsistent with findings from another study by Chiu et al. [ 13 ]. But Meij et al. [ 21 ] found a significant increase in the abundance of Proteobacteria in children with refractory constipation, which is consistent with our findings. These results indicate that they increased Proteobacteria abundance is correlated with FC. Similar to a study by Meij et al.[ 21 ], we found that the abundance of Bifidobacterium (4.21 ± 6.31) was elevated in the gut of disease group, while the abundance of Ruminococcus was decreased. Moreover, the abundance of opportunistic pathogenic bacteria such as Veillonella ( Veillonella_parvula , Veillonella_dispar ), Escherichia/Shigella, Klebsiella ( Klebsiella_pneumoniae ) and Streptococcus in the gut of disease group were increased. Previously, we found that the abundance of Bifidobacterium in the gut of children with cerebral palsy and FC was increased while that of Bifidobacteria was decreased after improvement in FC[ 22 ]. Interestingly, the abundance of Bifidobacterium-longum (0.02 ± 0.12) in the gut of the disease group in our study was markedly decreased. Guerra et al. [ 23 ] found that supplementing Bifidobacterium-longum in FC children improved defecation frequency and abdominal pain. These results suggest that the decrease in Bifidobacterium longum abundance may be related to FC, while the abundance of Bifidobacterium subtypes was increased in children in the disease group. This finding need to be verified through metagenomic sequencing. Elevated Veillonella parvula, Escherichia/Shigella may induce chronic inflammation in the intestines[24; 25], Klebsiella_pneumoniae and Streptococcus may cause respiratory tract infections[26; 27]. In addition, the abundance of Bacteroides thetaiotaomicron in the intestines of children in the disease group increased, possibly due to alteration to the composition of intestinal microbiota, increased intestinal and hepatic folate levels and metabolites, reducing metabolic dysfunction, and may be a protective strain [ 28 ]. However, its abundance was significantly lower than that of Bacteroides uniformis (0.66 ± 1.06 vs 2.85 ± 5.53). Compared with participants in the healthy group, the abundance of Bacteroides ( Bacteroides_uniformis ), Faecalibacterium ( Faecalibacterium_prausnitzii ), Ruminococcus,Kineothrix ( Kineothrix_alysoides ), Anaerostipes ( Anaerostipes_hadrus ) in the disease group was significantly decreased. Bacteroides and Ruminococcus decompose carbohydrates, improve the intestinal mucosal barrier function[29; 30]. Ruminococcus can prevent the development of allergies[ 29 ]. Bacteroides_uniformis increases the abundance of beneficial bacteria in the intestine, reduces the abundance of Escherichia Shigella , and affects immune function by modulating the bile acid metabolism [ 31 ]. Faecalibacterium_prausnitzii is one of the important producers of butyric acid [ 32 ], Ruminococcus, Kineothrix_alysoides and Anaerostipes_hadrus can also generate butyrates [29; 33; 34], affects T cell count[ 28 ]. Butyrates serve as a source of energy in the intestines and protects the mucosal barrier and regulates the immune function thereby regulating the human health [ 35 ]. The changes in the above-mentioned bacterial genera may be caused by downregulation of GM functions in diseases group, such as Metabolic-Diseases and Immune_System. The above results indicate that dysregulation of GM in the disease group causes chronic inflammation in the intestine, impairing immune function, and increasing the recurrence of respiratory infections, chronic cough, FC, among other conditions. 4.2Changes in GM composition and function can guide dietary adjustments and clinical interventions The above data show that the abundance of Bifidobacterium in the intestine of the disease group increased, while the abundance of Ruminococcus and Bacteroides decreased. In our previous study, we found a significant increase in the abundance of Bifidobacterium in children’s intestines, which was linked to excessive milk intake[ 22 ]. Notably, Ruminococcus and Bacteroides are carbohydrate degrading bacterial genera [29; 30]. The abundance of some GM functional pathways was decreased in the disease group, including carbohydrate metabolism, lipid metabolism, Transport_and_Catabolism. These changes in the GM composition and function illustrate that children should reduce the intake of milk and consume more vegetables, fruits, as well as high-fat foods. In this study, the abundance of butyrate producing bacteria such as Faecalibacterium-prausnitzii, Ruminococcus, Kineothrix lysoides and Anaerostipes_hadrus in the gut of children in the disease group was reduced, suggesting that such children may benefit from supplementation of butyrate-producing probiotics[29; 32–34]. In addition, considering that Bifidobacterium longum can improve FC[ 23 ], Bifidobacterium longum supplementation may benefit this group, but the application of other Bifidobacterium subspecies should be done with caution. The abundance of carbohydrate degrading bacteria such as Bacteroides and Ruminococcus in the gut of children in the disease group decreased has been reported to be decreased[29; 30]. Moreover, considering that carbohydrate metabolism was downregulated in the intestines, we recommend the use of dietary fiber supplementation (prebiotics) to alleviate disease developement. 4.3 GM is closely related to clinical phenotype Further, correlation analysis was conducted between gut microbiota and clinical phenotype, and the results showed that there was a significant correlation between multiple bacterial genera and allergic symptoms, allergens (dust mites), and FC. For instance, Haemophilus was significantly positively correlated with FC, whereas Megamonas, Butyrisimonas, and nasal congestion were significantly negatively correlated. Therefore, dysregulation of GM may induce or exacerbate AR and FC. 5. Conclusion In summary, the abundance of opportunistic pathogenic bacteria such as Veillonella, Escherichia/Shigella, Klebsiella , and Streptococcus in the gut of children in the disease group was increased, while the abundance of butyric acid-producing bacteria such as Faecalibacterium-prausnitzii, Ruminococcus, Kineothrix lysoides and Anaerostipes_hadrus was decreased, and the abundance of carbohydrate degrading bacteria such as Bacteroides and Ruminococcus also decreased, leading to a decline in the abundance of GM functions such as carbohydrate metabolism, lipid metabolism, metabolic diseases, and ImmuneSystem. Analysis of the GM composition and function in the disease group implied that supplementation of probiotics that produce butyric acid and dietary fiber (prebiotics) may correct dysregulation of GM, thereby improve AR and FC symptoms. In addition, we suggest that the disease group should be supplemented with Bifidobacteria . Meanwhile, we believe that children should reduce milk intake, eat more vegetables, fruits, and high-fat foods. Declarations Ethics statement This study was approved by the ethics committee of Longgang District Maternity & Child Healthcare Hospital of Shenzhen city with the registration number of LGFYKYXMMLL-2023-1. The parents, as legal guardians, voluntarily accepted scientific research on their children's care.Our Research have been performed in accordance with theDeclaration of Helsinki. Data Availability Statement The data set generated in this study can be accessed from the NCBI Sequence Archive (SRA) database,the direct link:https://dataview.ncbi.nlm.nih.gov/object/PRJNA1103935?reviewer= 8ia81sf9papv0kd3vt99i69ir6,its number is PRJNA1103935.Corresponding author should be contacted if someone wants to request the data from this study. Author contributions Zhenyu Yang, Congfu Huang and Chunyan Wang manage the project. Conceptualization, Congfu Huang and Chunyan Wang; Data curation, Zhenyu Yang and Weikeng Yang; Formal analysis, Chunyan Wang and Dongming Meng; Funding acquisition, Congfu Huang and Chunyan Wang; Investigation, Bin Wu; Methodology, Congfu Huang, Zhenyu Yang and Chunyan Wang; Project administration, Congfu Huang; Resources, Congfu Huang and Bin Wu; Software, Zhenyu Yang and Wei Kong; Supervision, Weikeng Yang and Lili Xu; Validation, Chunyan Wang; Visualization, Chunyan Wang and Lili Xu; Writing-original draft, Congfu Huang; Writing-review & editing, Chunyan Wang and Zhenyu Yang.All the authors reviewed the manuscript. Funding This work has been strongly supported by Longgang District Science and technology innovation Bureau (LGWJ2023-038 andLGWJ20230-072), Key Medical Discipline in Longgang District, and Internal project of Shenzhen Maternity ＆ Child Healthcare Hospital（FYB2017004). Acknowledgements We thank all participants for their support. We thank the doctors and nurses of Longgang District Maternity & Child Healthcare Hospital (Shenzhen, China) for assisting the research team in clinical examination and fecal sample collection. We also thank the authors who made their data publicly available.The authors would like to thank all the reviewers who participated in the review, as well as MJEditor (www.mjeditor.com) for providing English editing services during the preparation of this manuscript. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. References Chang MY, Kim JW, Rhee CS (2015) The quality of health information on allergic rhinitis, rhinitis, and sinusitis available on the internet. Allergy Asthma Immunol Res 7:141-147.https://doi.org/10.4168/aair.2015.7.2.141. Subspecialty Group of Rhinology, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery, Subspecialty Group of Rhinology, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association.Chinese guideline for diagnosis and treatment of allergic rhinitis (2022, revision).Chin J Otorhinolaryngol Head Neck Surg.2022,57(2):8-31.https://doi.org/10.3760/cma.j.cn115330-20211228-00828. Yong L,Jing L.The application of probiotics in children with allergic rhinitis.Chin J Otorhinolaryngol Integ Med.2018,26(3):177-171.https://doi.org/10.16542/j.cnki.issn.1007-4856.2018.03.007. Bradshaw O, Foy R, Seal AK, Darling JC (2021) Childhood constipation. Bmj 375:e065046.https://doi.org/10.1136/bmj-2021-065046. Southwell BR (2020) Treatment of childhood constipation: a synthesis of systematic reviews and meta-analyses. Expert Rev Gastroenterol Hepatol 14:163-174. 2020;14:163-74.https://doi.org/10.1080/17474124.2020.1733974. Zuar LR, Thompson LA (2023) What Parents Should Know About Constipation in Children. JAMA Pediatr 177:216.https://doi.org/10.1001/jamapediatrics.2022.5280. Wu MC, Jan MS, Chiou JY, Wang YH, Wei JC (2020) Constipation might be associated with risk of allergic rhinitis: A nationwide population-based cohort study. PLoS One 15:e0239723. 2020;15:e0239723.https://doi.org/10.1371/journal.pone.0239723. Walker S, Khan-Wasti S, Fletcher M, Cullinan P, Harris J, Sheikh A (2007) Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case-control study. J Allergy Clin Immunol 120:381-387.https://doi.org/10.1016/j.jaci.2007.03.034. Vriesman MH, Rajindrajith S, Koppen IJN, van Etten-Jamaludin FS, van Dijk M, Devanarayana NM, Tabbers MM, Benninga MA (2019) Quality of Life in Children with Functional Constipation: A Systematic Review and Meta-Analysis. J Pediatr 214:141-150.https://doi.org/10.1016/j.jpeds.2019.06.059. Shahbazi R, Yasavoli-Sharahi H, Alsadi N, Ismail N, Matar C (2020) Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders. Molecules 25.https://doi.org/10.3390/molecules25214891. Zheng XL, Yang Y, Wang BJ, Wang J, Tang HQ (2017) Synchronous dynamic research on respiratory and intestinal microflora of chronic bronchitis rat model. Chin J Integr Med 23:196-200.https://doi.org/10.1007/s11655-016-2731-7. Li MM, Zhou Y, Zuo L, Nie D, Li XA (2021) Dietary fiber regulates intestinal flora and suppresses liver and systemic inflammation to alleviate liver fibrosis in mice. Nutrition 81:110959.https://doi.org/10.1016/j.nut.2020.110959. Chiu CY, Chan YL, Tsai MH, Wang CJ, Chiang MH, Chiu CC (2019) Gut microbial dysbiosis is associated with allergen-specific IgE responses in young children with airway allergies. World Allergy Organ J 12:100021.https://doi.org/10.1016/j.waojou.2019.100021. Hu B, Kuang Y, Jing Y, Li Y, Zhao H, Ouyang H (2021) Pediatric allergic rhinitis with functional gastrointestinal disease: Associations with the intestinal microbiota and gastrointestinal peptides and therapeutic effects of interventions. Hum Exp Toxicol 40:2012-2021.https://doi.org/10.1177/09603271211017325. Vernon-Roberts A, Alexander I, Day AS (2021) Systematic Review of Pediatric Functional Gastrointestinal Disorders (Rome IV Criteria). J Clin Med 10.https://doi.org/10.3390/jcm10215087. Kaczynska A, Klosinska M, Chmiel P, Janeczek K, Emeryk A (2022) The Crosstalk between the Gut Microbiota Composition and the Clinical Course of Allergic Rhinitis: The Use of Probiotics, Prebiotics and Bacterial Lysates in the Treatment of Allergic Rhinitis. Nutrients 14.https://doi.org/10.3390/nu14204328. Fiocchi A, Cabana MD, Mennini M (2022) Current Use of Probiotics and Prebiotics in Allergy. J Allergy Clin Immunol Pract 10:2219-2242.https://doi.org/10.1016/j.jaip.2022.06.038. Lai H, Li Y, He Y, Chen F, Mi B, Li J, Xie J, Ma G, Yang J, Xu K, Liao X, Yin Y, Liang J, Kong L, Wang X, Li Z, Shen Y, Dang S, Zhang L, Wu Q, Zeng L, Shi L, Zhang X, Tian T, Liu X (2023) Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial. Gut Microbes 15:2197837.https://doi.org/10.1080/19490976.2023.2197837. Ford AC, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, Soffer EE, Spiegel BM, Moayyedi P (2014) Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 109:1547-1561; quiz 1546, 1562.https://doi.org/10.1038/ajg.2014.202. Luo C, Peng S, Li M, Ao X, Liu Z (2022) The Efficacy and Safety of Probiotics for Allergic Rhinitis: A Systematic Review and Meta-Analysis. Front Immunol 13:848279.https://doi.org/10.3389/fimmu.2022.848279. de Meij TG, de Groot EF, Eck A, Budding AE, Kneepkens CM, Benninga MA, van Bodegraven AA, Savelkoul PH (2016) Characterization of Microbiota in Children with Chronic Functional Constipation. PLoS One 11:e0164731.https://doi.org/10.1371/journal.pone.0164731. Huang C, Lyu J, Chu C, Ge L, Peng Y, Yang Z, Xiong S, Wu B, Chen X, Zhang X (2022) Dietary fiber and probiotics based on gut microbiota targeting for functional constipation in children with cerebral palsy. Front Pediatr 10:1001789.https://doi.org/10.3389/fped.2022.1001789. Guerra PV, Lima LN, Souza TC, Mazochi V, Penna FJ, Silva AM, Nicoli JR, Guimarães EV (2011) Pediatric functional constipation treatment with Bifidobacterium-containing yogurt: a crossover, double-blind, controlled trial. World J Gastroenterol 17:3916-3921.https://doi.org/10.3748/wjg.v17.i34.3916. Rojas-Tapias DF, Brown EM, Temple ER, Onyekaba MA, Mohamed AMT, Duncan K, Schirmer M, Walker RL, Mayassi T, Pierce KA, Ávila-Pacheco J, Clish CB, Vlamakis H, Xavier RJ (2022) Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the intestine. Nat Microbiol 7:1673-1685.https://doi.org/10.1038/s41564-022-01224-7. Zhao J, Bai M, Ning X, Qin Y, Wang Y, Yu Z, Dong R, Zhang Y, Sun S (2022) Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA Nephropathy. J Am Soc Nephrol 33:2276-2292.https://doi.org/10.1681/ASN.2022020189. Martin RM, Bachman MA (2018) Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front Cell Infect Microbiol 8:4.https://doi.org/10.3389/fcimb.2018.00004. Mishra A, Nam GH, Gim JA, Lee HE, Jo A, Kim HS (2018) Current Challenges of Streptococcus Infection and Effective Molecular, Cellular, and Environmental Control Methods in Aquaculture. Mol Cells 41:495-505.https://doi.org/10.14348/molcells.2018.2154. Li H, Wang XK, Tang M, Lei L, Li JR, Sun H, Jiang J, Dong B, Li HY, Jiang JD, Peng ZG (2024) Bacteroides thetaiotaomicron ameliorates mouse hepatic steatosis through regulating gut microbial composition, gut-liver folate and unsaturated fatty acids metabolism. Gut Microbes 16:2304159.https://doi.org/10.1080/19490976.2024.2304159. Ahn JR, Lee SH, Kim B, Nam MH, Ahn YK, Park YM, Jeong SM, Park MJ, Song KB, Lee SY, Hong SJ (2022) Ruminococcus gnavus ameliorates atopic dermatitis by enhancing Treg cell and metabolites in BALB/c mice. Pediatr Allergy Immunol 33:e13678.https://doi.org/10.1111/pai.13678. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E (2012) Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3:289-306.https://doi.org/10.4161/gmic.19897. Yan Y, Lei Y, Qu Y, Fan Z, Zhang T, Xu Y, Du Q, Brugger D, Chen Y, Zhang K, Zhang E (2023) Bacteroides uniformis-induced perturbations in colonic microbiota and bile acid levels inhibit TH17 differentiation and ameliorate colitis developments. NPJ Biofilms Microbiomes 9:56.https://doi.org/10.1038/s41522-023-00420-5. Heinken A, Khan MT, Paglia G, Rodionov DA, Harmsen HJ, Thiele I (2014) Functional metabolic map of Faecalibacterium prausnitzii, a beneficial human gut microbe. J Bacteriol 196:3289-3302.https://doi.org/10.1128/JB.01780-14. Haas KN, Blanchard JL (2017) Kineothrix alysoides, gen. nov., sp. nov., a saccharolytic butyrate-producer within the family Lachnospiraceae. Int J Syst Evol Microbiol 67:402-410.https://doi.org/10.1099/ijsem.0.001643. Liu D, Xie LS, Lian S, Li K, Yang Y, Wang WZ, Hu S, Liu SJ, Liu C, He Z (2024) Anaerostipes hadrus, a butyrate-producing bacterium capable of metabolizing 5-fluorouracil. mSphere 9:e0081623.https://doi.org/10.1128/msphere.00816-23. Sasaki M, Suaini NHA, Afghani J, Heye KN, O'Mahony L, Venter C, Lauener R, Frei R, Roduit C (2024) Systematic review of the association between short chain fatty acids and allergic diseases. Allergy.https://doi.org/10.1111/all.16065. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-4493967","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":313398026,"identity":"fdd77f6e-aae8-4b92-957f-7173da91b77e","order_by":0,"name":"Zhenyu Yang","email":"","orcid":"","institution":"NanKai University","correspondingAuthor":false,"prefix":"","firstName":"Zhenyu","middleName":"","lastName":"Yang","suffix":""},{"id":313398027,"identity":"142ba5d7-5b10-4e95-80ba-257cd5394343","order_by":1,"name":"Chunyan Wang","email":"","orcid":"","institution":"Shantou University Medical College, Sami Medical Center(Fourth People's Hospital)","correspondingAuthor":false,"prefix":"","firstName":"Chunyan","middleName":"","lastName":"Wang","suffix":""},{"id":313398028,"identity":"712717d5-3911-42f0-be41-eeb6b62598cc","order_by":2,"name":"Weikeng Yang","email":"","orcid":"","institution":"Shantou University Medical College, Longgang District People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Weikeng","middleName":"","lastName":"Yang","suffix":""},{"id":313398029,"identity":"12bd8aae-2f45-43b6-b59a-104ed2854853","order_by":3,"name":"Dongming Meng","email":"","orcid":"","institution":"Longgang Maternity and Child Institute of Shantou University Medical College （Longgang District Maternity\u0026Child Healthcare Hospital of Shenzhen City）","correspondingAuthor":false,"prefix":"","firstName":"Dongming","middleName":"","lastName":"Meng","suffix":""},{"id":313398030,"identity":"b05cac83-5299-4696-8f94-89d21c4a6505","order_by":4,"name":"Wei Kong","email":"","orcid":"","institution":"Longgang Maternity and Child Institute of Shantou University Medical College （Longgang District Maternity\u0026Child Healthcare Hospital of Shenzhen City）","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Kong","suffix":""},{"id":313398031,"identity":"73de1d66-084e-4b7a-9555-f7966591309d","order_by":5,"name":"Lili Xu","email":"","orcid":"","institution":"Longgang Maternity and Child Institute of Shantou University Medical College （Longgang District Maternity\u0026Child Healthcare Hospital of Shenzhen City）","correspondingAuthor":false,"prefix":"","firstName":"Lili","middleName":"","lastName":"Xu","suffix":""},{"id":313398032,"identity":"bac3d888-e3c5-4eb0-bdae-086ad6f4a213","order_by":6,"name":"Bin Wu","email":"","orcid":"","institution":"Longgang Maternity and Child Institute of Shantou University Medical College （Longgang District Maternity\u0026Child Healthcare Hospital of Shenzhen City）","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Wu","suffix":""},{"id":313398033,"identity":"6db33578-27d6-417f-9d21-0d01651879c0","order_by":7,"name":"Congfu Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYBAC++Pthx9+/Pevnp94PWfOpBlLsB1IkGwgWsuNBAMJHqAWgwPE6mDsOQDScyfP+HjyBoYfFdsIa2FmbzzwoEDiWbHZmWcFjD1nbhPWwsYDssWAmXHbjRwg2UaEFh4JkLsSmBk3zyBWiwRYy4HDiRskiNViwAMMZMkGYEAD/XKQKL8YsIOissFGjr89eeODHxVEaEECJEQNQgupOkbBKBgFo2CEAABIz0Cme02kngAAAABJRU5ErkJggg==","orcid":"","institution":"Longgang Maternity and Child Institute of Shantou University Medical College （Longgang District Maternity\u0026Child Healthcare Hospital of Shenzhen City）","correspondingAuthor":true,"prefix":"","firstName":"Congfu","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2024-05-29 03:21:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4493967/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4493967/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58386269,"identity":"769d81a3-4dc0-4d96-bd28-e12b78a836fe","added_by":"auto","created_at":"2024-06-14 18:43:53","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":9612,"visible":true,"origin":"","legend":"\u003cp\u003eTwo groups of children GM α Diversity comparison\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4493967/v1/15ae26c287894bac187688b0.jpg"},{"id":58386270,"identity":"64f1fd37-4e54-4281-bdf2-ce3d0f9dc31e","added_by":"auto","created_at":"2024-06-14 18:43:53","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":25587,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of GM PCA between two groups of children\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4493967/v1/2d19aa48dc393734103aecf2.jpg"},{"id":58386271,"identity":"34d30c02-a697-4725-89f1-6f1c25ffca9e","added_by":"auto","created_at":"2024-06-14 18:43:53","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":121870,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the phylum and genera abundance between the two groups.Remarks: * indicates P\u0026lt;0.05, * * indicates P\u0026lt;0.01,statistically significant differences between the two groups. The higher the number ofasterisks, moresignificant the difference.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4493967/v1/20e09254a8546f2f93b4ca10.jpg"},{"id":58386274,"identity":"e6439cc9-fe92-4d10-9fe6-77d7c5bae493","added_by":"auto","created_at":"2024-06-14 18:43:53","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":90223,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of GM function between the two groups.Remarks: * indicates P\u0026lt;0.05, * * indicates P\u0026lt;0.01,statistically significantdifferences between the two groups. The higher the number of asterisks, more significant the difference.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4493967/v1/02b932b68f3f3de31c8c57f4.jpg"},{"id":58386273,"identity":"e980e584-234a-46bd-8a65-40e083bd1684","added_by":"auto","created_at":"2024-06-14 18:43:53","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":122228,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between GM and clinical phenotype in AR children.Legend description: A correlation analysis was performed with eleven clinical phenotypes and genera with a relative abundance of ≥ 0.1%. Results are shown as above where significance was expressed as *P\u0026lt;0.05 and **P\u0026lt;0.01.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4493967/v1/433c80b74e4d167b1a0ffb3a.jpg"},{"id":60697650,"identity":"9b59d00c-78ad-407e-8be0-976f6aec6648","added_by":"auto","created_at":"2024-07-19 16:52:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1157888,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4493967/v1/dc6ce7f0-ce9d-4e8f-9063-77516644b3da.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Gut microbiota composition and functional classification in preschool children with allergic rhinitis and functional constipation","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eAllergic rhinitis (AR) is a chronic inflammatory allergic disease affecting the nasal mucosa associated with Th1/Th2 imbalance following exposure to allergens. The secretion of cytokines such as IL-4 and IT-5 induced by Th2 cells, followed by the production of IgE leads to the emergence of chronic inflammation of nasal mucosa, manifesting as a runny nose, nasal congestion, sneezing, nasal itching and other symptoms. Currently, AR affects 40% of the global population, and the incidence of allergic diseases in children in China has been increasing in the past 20 year[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The most recent study found that the prevalence of AR in children in China has exceeded 20%, AR is associated with the development of several conditions, including upper airway cough syndrome, sinusitis, middle ear infections, adenoid hypertrophy, cough variant asthma, and gastroesophageal reflux [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Moreover, a considerable proportion of children with AR experience gastrointestinal symptoms, such as anorexia, poor appetite, FC, diarrhea, weight loss, anemia, and low vitamin D levels [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Studies have demonstrated that FC is often caused by a lack of dietary fiber, GM dysbiosis, among other factors [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. FC can cause anal fissures, rectal bleeding, impaction, painful defecation, tense defecation, and other phenomena, all which seriously affect the quality of life of AR children [8; 9], and FC can potentially increase the risk of AR [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eModern medicine has demonstrated that patients with respiratory system diseases often experience gastrointestinal diseases such as inflammatory bowel disease, and about 50% of inflammatory bowel disease patients manifest varying degrees of lung function damage, leading to the concept of the \"gut-lung axis\"[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Embryology research have revealed that the human lung and trachea are derived from the foregut of the primitive gut, and differentiate into respiratory epithelium and glands, suggesting that the structures of the gastrointestinal tract and respiratory tract share the same origin [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Respiratory diseases and antibiotic use can significantly alter the GM, affecting its diversity and composition. Conversely, various intestinal diseases, like ulcerative colitis, can sometimes cause respiratory symptoms and alterations in the microbes that reside in the lungs. Interestingly, research suggests that probiotics may be beneficial in alleviating respiratory allergic diseases[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough several studies have explored the relationship between AR and GM in adults, only two reports have reported this relationship in children. Chiu et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] investigated AR children aged 4.4\u0026ndash;6.8 years found that the abundance of \u003cem\u003eFirmicutes\u003c/em\u003e was decreased at the phylum level, and the abundance of genera such as \u003cem\u003eDialister\u003c/em\u003e and \u003cem\u003eDorea\u003c/em\u003e was also reduced. Hu et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] explored AR children with functional gastrointestinal disorders under the age of 3 and uncovered that these children had abnormal GM and abnormal intestinal endocrine hormones, and the two were correlated. While the link between GM and various health conditions has been explored extensively, there's a lack of research on GM in preschool children with AR who also experience FC. Our clinical observations suggested a higher prevalence of FC in preschoolers with AR. To investigate this further, we compared the gut microbiota composition and function between two groups of children: preschoolers with AR and FC, and healthy children of the same age.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Patients\u003c/h2\u003e \u003cp\u003ePatients who met the diagnostic criteria for AR in the \"Chinese guideline for diagnosis and treatment of allergic rhinitis (2022, revision)\" [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and the diagnostic criteria for FC in the New Roman IV system [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] were included in this study. Next, 32 AR and FC preschool children who were treated at Longgang District Maternity\u0026amp;Child Healthcare Hospital in Shenzhen from January 2022 to December 2023 were assigned to the disease group, and data of 21 healthy children of the same age (healthy group) obtained from published literature were used for comparison. We excluded children with the following conditions: severe liver disease, dysplasia, severe infections, and any antibiotic or microbial medication use within the month prior to sample collection. This study was approved by the ethics committee of Longgang District Maternity \u0026amp; Child Healthcare Hospital of Shenzhen city with the registration number of LGFYKYXMMLL-2023-1. The parents, as legal guardians, voluntarily accepted scientific research on their children's care, informed consent was obtained from the parents and their legal guardians.Our Research have been performed in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Sampling, sequencing and bioinformatics\u003c/h2\u003e \u003cp\u003e5 g central of midcourse feces were collected and frozen at -80℃ immediately. Total DNA was extracted using PowerSoil\u0026reg; DNA Isolation Kit (MoBio, USA) and amplified by 16S rDNA V3-V4 regions primers for next-generation sequencing (Illumina, USA). Raw sequencing data were subjected to quality control and assembled to tags using FLASH (v1.2.11), and were clustered to operational taxonomic units (OTUs). To classify the gut microbiota (GM), we used a reference database called Greengene (version 201305). This database helps us assign taxonomic labels (like genus and phylum) to the different microbes identified in the samples. In addition to classification, we also analyzed the predicted functions of the GM using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Finally, we compared variations in microbial communities (at the genus and phylum levels) between the different groups involved in the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistic analysis\u003c/h2\u003e \u003cp\u003eThe principle components analysis (PCA) was conducted using the ade4 package (v1.7-22) in R software (v3.3.3). Differences between different groups or subgroups were compared using the Wilcoxon sum-rank test at the taxonomic levels of genus and phylum, and at GM function. Correlation analysis was performed by Spearman coefficient between genus and clinical syndromes.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 The GM diversity was significantly increased in the disease group\u003c/h2\u003e \u003cp\u003eDifferences in GM diversity and composition between disease group and healthy children were analyzed and the results were as follows: 1) the GM α-diversity in disease group was significantly higher than that in healthy group (2.257\u0026thinsp;\u0026plusmn;\u0026thinsp;0.367 vs 1.980\u0026thinsp;\u0026plusmn;\u0026thinsp;0.352, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e); 2) PCA dimension reduction analysis showed that the GM composition in half of the disease group was similar to that in healthy children, but that of another disease group was different from that of healthy children. The main diverse genera were \u003cem\u003ePrevotella, Bacteroides\u003c/em\u003e, \u003cem\u003eAgathobacter, Parasutterella, Phocaeicola\u003c/em\u003e among others (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2 The phyla were different between disease group and healthy group\u003c/h2\u003e \u003cp\u003eThe top 5 phyla, which accounted for 99.45% and 99.80% proportion of GM in the disease group and healthy children, respectively, were selected. Compared to disease group, \u003cem\u003eBacteroidetes\u003c/em\u003e was significantly higher in the healthy group (p\u0026thinsp;=\u0026thinsp;0.045, Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), but \u003cem\u003eProteobacteria\u003c/em\u003e was decreased in healthy group (p\u0026thinsp;=\u0026thinsp;0, Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The differences of abundance of the remaining phyla were not significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnalysis of phyla in children from the disease and control groups (top 5)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTop 5 phyla\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDisease group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFDR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSD (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBacteroidetes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFirmicutes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e43.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.709\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.709\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eProteobacteria\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActinobacteria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVerrucomicrobia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.321\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.3 The dominant genus in disease group was different from that in healthy group\u003c/h2\u003e \u003cp\u003eThe top 11 bacterial genera were compared between the disease group and the healthy group, and the results that the abundance of the following microbiota was increased in the disease group: \u003cem\u003eBifidobacterium\u003c/em\u003e, \u003cem\u003ePhascolarctobacterium\u003c/em\u003e, \u003cem\u003eVeillonella\u003c/em\u003e, \u003cem\u003eEscherichia/Shigella\u003c/em\u003e, \u003cem\u003eKlebsiella,Streptococcus\u003c/em\u003e, among others. (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The genera with decreased abundance in disease group were \u003cem\u003eBacteroides, Faecalibacterium, Ruminococcus, Kineothrix, Anaerostipes\u003c/em\u003e. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the top 11 dominant genera in the two groups of children\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTop 11 dominant genus\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDisease group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFDR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSD(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBacteroides\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFaecalibacterium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBifidobacterium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRuminococcus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePhascolarctobacterium\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.262\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eEscherichia/Shigella\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.198\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eVeillonella\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKineothrix\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAnaerostipes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStreptococcus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.4 The dominant species in disease group was different from that in healthy group\u003c/h2\u003e \u003cp\u003eThe top 11 bacterial species were compared between the disease group and the healthy group, and the results showed a significant increase in abundance of the species in the disease group: \u003cem\u003eKlebsiella_pneumoniae\u003c/em\u003e, \u003cem\u003eBacteroides_thetaiotaomicron\u003c/em\u003e, \u003cem\u003eVeillonella_parvula\u003c/em\u003e, \u003cem\u003eVeillonella_dispar, Flavonifractor_plautii\u003c/em\u003e (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The species that showed decreased abundance in disease group included: \u003cem\u003eFaecalibacterium_prausnitzii, Bacteroides_uniformis, Kineothrix_alysoides, Bifidobacterium_longum\u003c/em\u003e, and \u003cem\u003eAnaerostipes_hadrus\u003c/em\u003e. (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the top 11 dominant species in the two groups of children\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTop 11 dominant genus\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDisease group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFDR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSD(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFaecalibacterium_prausnitzii\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBacteroides_uniformis\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKlebsiella_pneumoniae\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eKineothrix_alysoides\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBifidobacterium_longum\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAnaerostipes_hadrus\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.079\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eBacteroides_thetaiotaomicron\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eVeillonella_parvula\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eVeillonella_dispar\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFlavonifractor_plautii\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eFaecalibacterium_prausnitzii\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.5 There were differences in GM function between disease group and healthy group\u003c/h2\u003e \u003cp\u003eDifferences in GM composition can alter the function of flora. Therefore, we analyzed differences in GM function between children in the disease group and the healthy group. Compared with the healthy children group, the abundance of functional genes related to genetic information processing and Xenobiotics_Biodegradation_and_Metabolism was significantly higher in the disease group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The abundance of functional pathway related to carbohydrate metabolism, lipid metabolism, Transport_and_Catabolism, Endocrine_System, Nervous_System, Metabolic_Diseases and Immune_System was significantly lower (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.6 GM in children with AR is correlated with clinical phenotype\u003c/h2\u003e \u003cp\u003eTo investigate whether GM changes can alter the development of clinical symptoms of AR, we analyzed the correlation between GM and the clinical phenotype of children in the disease group. It was observed that the genera that were negatively correlated with allergy sources such as house dust mite were \u003cem\u003eBlautia, Fusicatenibacter\u003c/em\u003e, and \u003cem\u003eRuminococcus\u003c/em\u003e. The genus \u003cem\u003ePhocaeicola\u003c/em\u003e was positively correlated with skin allergies such as eczema, while the genus \u003cem\u003eLachnospira\u003c/em\u003e was negatively correlated. The genus \u003cem\u003eHaemophilus\u003c/em\u003e showed a positive relationship with FC, while \u003cem\u003eDysosmobacter\u003c/em\u003e and \u003cem\u003eFlintibacter\u003c/em\u003e were negatively correlated. The genus that showed a negative associated with snoring was \u003cem\u003ePrevotella\u003c/em\u003e. Moreover, \u003cem\u003ePhocaeicola\u003c/em\u003e, \u003cem\u003eVeillonella\u003c/em\u003e and \u003cem\u003eMediterraneibacter\u003c/em\u003e were negatively associated with nose picking and nose rubbing. The genus that showed a positive correlation with runny nose was \u003cem\u003eAnaerotignum\u003c/em\u003e and that with a negative correlation with runny nose was \u003cem\u003eDorea\u003c/em\u003e. The genus that showed a positive correlation with nasal congestion was \u003cem\u003eHaemophilus\u003c/em\u003e, while those with a negative correlation were \u003cem\u003eMegamonas, Ruthenibacterium, Eisenbergiella, Coprococcus\u003c/em\u003e and \u003cem\u003eButyricimonas\u003c/em\u003e. \u003cem\u003eStreptococcus\u003c/em\u003e was positively correlated with sneezing, while \u003cem\u003eMegamonas\u003c/em\u003e and \u003cem\u003eAkkermansia\u003c/em\u003e were negatively correlated. The genera that were negatively associated with recurrent cough were \u003cem\u003eLachnospiracea incertae sedis, Ligilactobacillus, Erysipelatoclostridium\u003c/em\u003e and \u003cem\u003eIntestinibacter\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eAllergic rhinitis (AR) is a prevalent condition in children. It can trigger a cascade of bothersome symptoms, including frequent respiratory infections, chronic cough, functional constipation (FC), and other complications [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. These issues can significantly impact a child's quality of life[8; 9]. AR is often treated with antihistamines, leukotriene receptor antagonists, and nasal corticosteroids, while FC is mainly treated with laxatives such as lactulose and glycerin. However, recent studies have indicated that AR, FC, and dysbiosis of GM are closely related[13; 14]. Elsewhere, supplementation of probiotics and prebiotics based on GM was found to improve symptoms of AR and FC [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, there is no consensus on how to select appropriate types of probiotics and prebiotics for these children [19; 20].\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Dysfunction of GM leading to chronic inflammation, inducing or exacerbating AR and FC\u003c/h2\u003e \u003cp\u003eIn this study, the disease group experienced the GM disorder, whereas the abundance of \u003cem\u003eBacteroidetes\u003c/em\u003e in the phyla was significantly reduced, while that of \u003cem\u003eProteobacteria\u003c/em\u003e was significantly increased, which is inconsistent with findings from another study by Chiu et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. But Meij et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] found a significant increase in the abundance of \u003cem\u003eProteobacteria\u003c/em\u003e in children with refractory constipation, which is consistent with our findings. These results indicate that they increased \u003cem\u003eProteobacteria\u003c/em\u003e abundance is correlated with FC.\u003c/p\u003e \u003cp\u003eSimilar to a study by Meij et al.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], we found that the abundance of \u003cem\u003eBifidobacterium\u003c/em\u003e (4.21\u0026thinsp;\u0026plusmn;\u0026thinsp;6.31) was elevated in the gut of disease group, while the abundance of \u003cem\u003eRuminococcus\u003c/em\u003e was decreased. Moreover, the abundance of opportunistic pathogenic bacteria such as \u003cem\u003eVeillonella\u003c/em\u003e (\u003cem\u003eVeillonella_parvula\u003c/em\u003e, \u003cem\u003eVeillonella_dispar\u003c/em\u003e), \u003cem\u003eEscherichia/Shigella, Klebsiella\u003c/em\u003e (\u003cem\u003eKlebsiella_pneumoniae\u003c/em\u003e) and \u003cem\u003eStreptococcus\u003c/em\u003e in the gut of disease group were increased. Previously, we found that the abundance of \u003cem\u003eBifidobacterium\u003c/em\u003e in the gut of children with cerebral palsy and FC was increased while that of \u003cem\u003eBifidobacteria\u003c/em\u003e was decreased after improvement in FC[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Interestingly, the abundance of \u003cem\u003eBifidobacterium-longum\u003c/em\u003e (0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12) in the gut of the disease group in our study was markedly decreased. Guerra et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] found that supplementing \u003cem\u003eBifidobacterium-longum\u003c/em\u003e in FC children improved defecation frequency and abdominal pain. These results suggest that the decrease in \u003cem\u003eBifidobacterium longum\u003c/em\u003e abundance may be related to FC, while the abundance of \u003cem\u003eBifidobacterium\u003c/em\u003e subtypes was increased in children in the disease group. This finding need to be verified through metagenomic sequencing. Elevated \u003cem\u003eVeillonella parvula, Escherichia/Shigella\u003c/em\u003e may induce chronic inflammation in the intestines[24; 25], \u003cem\u003eKlebsiella_pneumoniae\u003c/em\u003e and \u003cem\u003eStreptococcus\u003c/em\u003e may cause respiratory tract infections[26; 27]. In addition, the abundance of \u003cem\u003eBacteroides thetaiotaomicron\u003c/em\u003e in the intestines of children in the disease group increased, possibly due to alteration to the composition of intestinal microbiota, increased intestinal and hepatic folate levels and metabolites, reducing metabolic dysfunction, and may be a protective strain [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, its abundance was significantly lower than that of \u003cem\u003eBacteroides uniformis\u003c/em\u003e (0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06 vs 2.85\u0026thinsp;\u0026plusmn;\u0026thinsp;5.53).\u003c/p\u003e \u003cp\u003eCompared with participants in the healthy group, the abundance of \u003cem\u003eBacteroides\u003c/em\u003e (\u003cem\u003eBacteroides_uniformis\u003c/em\u003e), \u003cem\u003eFaecalibacterium\u003c/em\u003e (\u003cem\u003eFaecalibacterium_prausnitzii\u003c/em\u003e), \u003cem\u003eRuminococcus,Kineothrix\u003c/em\u003e (\u003cem\u003eKineothrix_alysoides\u003c/em\u003e), \u003cem\u003eAnaerostipes\u003c/em\u003e (\u003cem\u003eAnaerostipes_hadrus\u003c/em\u003e) in the disease group was significantly decreased. \u003cem\u003eBacteroides\u003c/em\u003e and \u003cem\u003eRuminococcus\u003c/em\u003e decompose carbohydrates, improve the intestinal mucosal barrier function[29; 30]. \u003cem\u003eRuminococcus\u003c/em\u003e can prevent the development of allergies[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. \u003cem\u003eBacteroides_uniformis\u003c/em\u003e increases the abundance of beneficial bacteria in the intestine, reduces the abundance of \u003cem\u003eEscherichia Shigella\u003c/em\u003e, and affects immune function by modulating the bile acid metabolism [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. \u003cem\u003eFaecalibacterium_prausnitzii\u003c/em\u003e is one of the important producers of butyric acid [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], \u003cem\u003eRuminococcus, Kineothrix_alysoides\u003c/em\u003e and \u003cem\u003eAnaerostipes_hadrus\u003c/em\u003e can also generate butyrates [29; 33; 34], affects T cell count[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Butyrates serve as a source of energy in the intestines and protects the mucosal barrier and regulates the immune function thereby regulating the human health [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The changes in the above-mentioned bacterial genera may be caused by downregulation of GM functions in diseases group, such as Metabolic-Diseases and Immune_System. The above results indicate that dysregulation of GM in the disease group causes chronic inflammation in the intestine, impairing immune function, and increasing the recurrence of respiratory infections, chronic cough, FC, among other conditions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.2Changes in GM composition and function can guide dietary adjustments and clinical interventions\u003c/h2\u003e \u003cp\u003eThe above data show that the abundance of \u003cem\u003eBifidobacterium\u003c/em\u003e in the intestine of the disease group increased, while the abundance of \u003cem\u003eRuminococcus\u003c/em\u003e and \u003cem\u003eBacteroides\u003c/em\u003e decreased. In our previous study, we found a significant increase in the abundance of \u003cem\u003eBifidobacterium\u003c/em\u003e in children\u0026rsquo;s intestines, which was linked to excessive milk intake[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Notably, \u003cem\u003eRuminococcus\u003c/em\u003e and \u003cem\u003eBacteroides\u003c/em\u003e are carbohydrate degrading bacterial genera [29; 30]. The abundance of some GM functional pathways was decreased in the disease group, including carbohydrate metabolism, lipid metabolism, Transport_and_Catabolism. These changes in the GM composition and function illustrate that children should reduce the intake of milk and consume more vegetables, fruits, as well as high-fat foods.\u003c/p\u003e \u003cp\u003eIn this study, the abundance of butyrate producing bacteria such as \u003cem\u003eFaecalibacterium-prausnitzii, Ruminococcus, Kineothrix lysoides\u003c/em\u003e and \u003cem\u003eAnaerostipes_hadrus\u003c/em\u003e in the gut of children in the disease group was reduced, suggesting that such children may benefit from supplementation of butyrate-producing probiotics[29; 32\u0026ndash;34]. In addition, considering that \u003cem\u003eBifidobacterium longum\u003c/em\u003e can improve FC[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], \u003cem\u003eBifidobacterium longum\u003c/em\u003e supplementation may benefit this group, but the application of other Bifidobacterium subspecies should be done with caution. The abundance of carbohydrate degrading bacteria such as \u003cem\u003eBacteroides\u003c/em\u003e and \u003cem\u003eRuminococcus\u003c/em\u003e in the gut of children in the disease group decreased has been reported to be decreased[29; 30]. Moreover, considering that carbohydrate metabolism was downregulated in the intestines, we recommend the use of dietary fiber supplementation (prebiotics) to alleviate disease developement.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e4.3 GM is closely related to clinical phenotype\u003c/h2\u003e \u003cp\u003eFurther, correlation analysis was conducted between gut microbiota and clinical phenotype, and the results showed that there was a significant correlation between multiple bacterial genera and allergic symptoms, allergens (dust mites), and FC. For instance, Haemophilus was significantly positively correlated with FC, whereas Megamonas, Butyrisimonas, and nasal congestion were significantly negatively correlated. Therefore, dysregulation of GM may induce or exacerbate AR and FC.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn summary, the abundance of opportunistic pathogenic bacteria such as \u003cem\u003eVeillonella, Escherichia/Shigella, Klebsiella\u003c/em\u003e, and \u003cem\u003eStreptococcus\u003c/em\u003e in the gut of children in the disease group was increased, while the abundance of butyric acid-producing bacteria such as \u003cem\u003eFaecalibacterium-prausnitzii, Ruminococcus, Kineothrix lysoides\u003c/em\u003e and \u003cem\u003eAnaerostipes_hadrus\u003c/em\u003e was decreased, and the abundance of carbohydrate degrading bacteria such as \u003cem\u003eBacteroides\u003c/em\u003e and \u003cem\u003eRuminococcus\u003c/em\u003e also decreased, leading to a decline in the abundance of GM functions such as carbohydrate metabolism, lipid metabolism, metabolic diseases, and ImmuneSystem. Analysis of the GM composition and function in the disease group implied that supplementation of probiotics that produce butyric acid and dietary fiber (prebiotics) may correct dysregulation of GM, thereby improve AR and FC symptoms. In addition, we suggest that the disease group should be supplemented with \u003cem\u003eBifidobacteria\u003c/em\u003e. Meanwhile, we believe that children should reduce milk intake, eat more vegetables, fruits, and high-fat foods.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the ethics committee of Longgang District Maternity \u0026amp; Child Healthcare Hospital of Shenzhen city with the registration number of LGFYKYXMMLL-2023-1. The parents, as legal guardians, voluntarily accepted scientific research on their children\u0026apos;s care.Our Research have been performed in accordance with theDeclaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data set generated in this study can be accessed from the NCBI Sequence Archive (SRA) database,the direct link:https://dataview.ncbi.nlm.nih.gov/object/PRJNA1103935?reviewer=\u003c/p\u003e\n\u003cp\u003e8ia81sf9papv0kd3vt99i69ir6,its number is PRJNA1103935.Corresponding author\u0026nbsp;should be contacted if someone wants to request the data from this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZhenyu Yang, Congfu Huang and\u0026nbsp;Chunyan Wang\u0026nbsp;manage the project. Conceptualization, Congfu Huang and\u0026nbsp;Chunyan Wang; Data curation, Zhenyu Yang and\u0026nbsp;Weikeng Yang; Formal analysis,\u0026nbsp;Chunyan Wang\u0026nbsp;and\u0026nbsp;Dongming Meng; Funding acquisition, Congfu Huang and\u0026nbsp;Chunyan Wang; Investigation,\u0026nbsp;Bin Wu; Methodology, Congfu Huang,\u0026nbsp;Zhenyu Yang\u0026nbsp;and\u0026nbsp;Chunyan Wang; Project administration, Congfu Huang; Resources, Congfu Huang and\u0026nbsp;Bin Wu; Software,\u0026nbsp;Zhenyu Yang and Wei Kong; Supervision,\u0026nbsp;Weikeng Yang\u0026nbsp;and\u0026nbsp;Lili Xu; Validation,\u0026nbsp;Chunyan Wang; Visualization,\u0026nbsp;Chunyan Wang and Lili Xu; Writing-original draft, Congfu Huang; Writing-review \u0026amp; editing,\u0026nbsp;Chunyan Wang and\u0026nbsp;Zhenyu Yang.All the authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work has been strongly supported by Longgang District Science and technology innovation Bureau (LGWJ2023-038 andLGWJ20230-072), Key Medical Discipline in Longgang District,\u0026nbsp;and Internal project of\u0026nbsp;Shenzhen Maternity\u0026nbsp;＆\u0026nbsp;Child Healthcare Hospital（FYB2017004).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all participants for their support. We thank the doctors and nurses of\u0026nbsp;Longgang District Maternity \u0026amp; Child Healthcare Hospital\u0026nbsp;(Shenzhen, China) for assisting the research team in clinical examination and fecal sample collection. We also thank the authors who made their data publicly available.The authors would like to thank all the reviewers who participated in the review, as well as MJEditor (www.mjeditor.com) for providing English editing services during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChang MY, Kim JW, Rhee CS (2015) The quality of health information on allergic rhinitis, rhinitis, and sinusitis available on the internet. Allergy Asthma Immunol Res 7:141-147.https://doi.org/10.4168/aair.2015.7.2.141.\u003c/li\u003e\n\u003cli\u003eSubspecialty Group of Rhinology, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery, Subspecialty Group of Rhinology, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association.Chinese guideline for diagnosis and treatment of allergic rhinitis (2022, revision).Chin J Otorhinolaryngol Head Neck Surg.2022,57(2):8-31.https://doi.org/10.3760/cma.j.cn115330-20211228-00828.\u003c/li\u003e\n\u003cli\u003eYong L,Jing L.The application of probiotics in children with allergic rhinitis.Chin J Otorhinolaryngol Integ Med.2018,26(3):177-171.https://doi.org/10.16542/j.cnki.issn.1007-4856.2018.03.007.\u003c/li\u003e\n\u003cli\u003eBradshaw O, Foy R, Seal AK, Darling JC (2021) Childhood constipation. Bmj 375:e065046.https://doi.org/10.1136/bmj-2021-065046.\u003c/li\u003e\n\u003cli\u003eSouthwell BR (2020) Treatment of childhood constipation: a synthesis of systematic reviews and meta-analyses. Expert Rev Gastroenterol Hepatol 14:163-174. 2020;14:163-74.https://doi.org/10.1080/17474124.2020.1733974.\u003c/li\u003e\n\u003cli\u003eZuar LR, Thompson LA (2023) What Parents Should Know About Constipation in Children. JAMA Pediatr 177:216.https://doi.org/10.1001/jamapediatrics.2022.5280.\u003c/li\u003e\n\u003cli\u003eWu MC, Jan MS, Chiou JY, Wang YH, Wei JC (2020) Constipation might be associated with risk of allergic rhinitis: A nationwide population-based cohort study. PLoS One 15:e0239723. 2020;15:e0239723.https://doi.org/10.1371/journal.pone.0239723.\u003c/li\u003e\n\u003cli\u003eWalker S, Khan-Wasti S, Fletcher M, Cullinan P, Harris J, Sheikh A (2007) Seasonal allergic rhinitis is associated with a detrimental effect on examination performance in United Kingdom teenagers: case-control study. J Allergy Clin Immunol 120:381-387.https://doi.org/10.1016/j.jaci.2007.03.034.\u003c/li\u003e\n\u003cli\u003eVriesman MH, Rajindrajith S, Koppen IJN, van Etten-Jamaludin FS, van Dijk M, Devanarayana NM, Tabbers MM, Benninga MA (2019) Quality of Life in Children with Functional Constipation: A Systematic Review and Meta-Analysis. J Pediatr 214:141-150.https://doi.org/10.1016/j.jpeds.2019.06.059.\u003c/li\u003e\n\u003cli\u003eShahbazi R, Yasavoli-Sharahi H, Alsadi N, Ismail N, Matar C (2020) Probiotics in Treatment of Viral Respiratory Infections and Neuroinflammatory Disorders. Molecules 25.https://doi.org/10.3390/molecules25214891.\u003c/li\u003e\n\u003cli\u003eZheng XL, Yang Y, Wang BJ, Wang J, Tang HQ (2017) Synchronous dynamic research on respiratory and intestinal microflora of chronic bronchitis rat model. Chin J Integr Med 23:196-200.https://doi.org/10.1007/s11655-016-2731-7. \u003c/li\u003e\n\u003cli\u003eLi MM, Zhou Y, Zuo L, Nie D, Li XA (2021) Dietary fiber regulates intestinal flora and suppresses liver and systemic inflammation to alleviate liver fibrosis in mice. Nutrition 81:110959.https://doi.org/10.1016/j.nut.2020.110959.\u003c/li\u003e\n\u003cli\u003eChiu CY, Chan YL, Tsai MH, Wang CJ, Chiang MH, Chiu CC (2019) Gut microbial dysbiosis is associated with allergen-specific IgE responses in young children with airway allergies. World Allergy Organ J 12:100021.https://doi.org/10.1016/j.waojou.2019.100021.\u003c/li\u003e\n\u003cli\u003eHu B, Kuang Y, Jing Y, Li Y, Zhao H, Ouyang H (2021) Pediatric allergic rhinitis with functional gastrointestinal disease: Associations with the intestinal microbiota and gastrointestinal peptides and therapeutic effects of interventions. Hum Exp Toxicol 40:2012-2021.https://doi.org/10.1177/09603271211017325.\u003c/li\u003e\n\u003cli\u003eVernon-Roberts A, Alexander I, Day AS (2021) Systematic Review of Pediatric Functional Gastrointestinal Disorders (Rome IV Criteria). J Clin Med 10.https://doi.org/10.3390/jcm10215087.\u003c/li\u003e\n\u003cli\u003eKaczynska A, Klosinska M, Chmiel P, Janeczek K, Emeryk A (2022) The Crosstalk between the Gut Microbiota Composition and the Clinical Course of Allergic Rhinitis: The Use of Probiotics, Prebiotics and Bacterial Lysates in the Treatment of Allergic Rhinitis. Nutrients 14.https://doi.org/10.3390/nu14204328.\u003c/li\u003e\n\u003cli\u003eFiocchi A, Cabana MD, Mennini M (2022) Current Use of Probiotics and Prebiotics in Allergy. J Allergy Clin Immunol Pract 10:2219-2242.https://doi.org/10.1016/j.jaip.2022.06.038.\u003c/li\u003e\n\u003cli\u003eLai H, Li Y, He Y, Chen F, Mi B, Li J, Xie J, Ma G, Yang J, Xu K, Liao X, Yin Y, Liang J, Kong L, Wang X, Li Z, Shen Y, Dang S, Zhang L, Wu Q, Zeng L, Shi L, Zhang X, Tian T, Liu X (2023) Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial. Gut Microbes 15:2197837.https://doi.org/10.1080/19490976.2023.2197837.\u003c/li\u003e\n\u003cli\u003eFord AC, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, Soffer EE, Spiegel BM, Moayyedi P (2014) Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis. Am J Gastroenterol 109:1547-1561; quiz 1546, 1562.https://doi.org/10.1038/ajg.2014.202.\u003c/li\u003e\n\u003cli\u003eLuo C, Peng S, Li M, Ao X, Liu Z (2022) The Efficacy and Safety of Probiotics for Allergic Rhinitis: A Systematic Review and Meta-Analysis. Front Immunol 13:848279.https://doi.org/10.3389/fimmu.2022.848279.\u003c/li\u003e\n\u003cli\u003ede Meij TG, de Groot EF, Eck A, Budding AE, Kneepkens CM, Benninga MA, van Bodegraven AA, Savelkoul PH (2016) Characterization of Microbiota in Children with Chronic Functional Constipation. PLoS One 11:e0164731.https://doi.org/10.1371/journal.pone.0164731.\u003c/li\u003e\n\u003cli\u003eHuang C, Lyu J, Chu C, Ge L, Peng Y, Yang Z, Xiong S, Wu B, Chen X, Zhang X (2022) Dietary fiber and probiotics based on gut microbiota targeting for functional constipation in children with cerebral palsy. Front Pediatr 10:1001789.https://doi.org/10.3389/fped.2022.1001789.\u003c/li\u003e\n\u003cli\u003eGuerra PV, Lima LN, Souza TC, Mazochi V, Penna FJ, Silva AM, Nicoli JR, Guimar\u0026atilde;es EV (2011) Pediatric functional constipation treatment with Bifidobacterium-containing yogurt: a crossover, double-blind, controlled trial. World J Gastroenterol 17:3916-3921.https://doi.org/10.3748/wjg.v17.i34.3916.\u003c/li\u003e\n\u003cli\u003eRojas-Tapias DF, Brown EM, Temple ER, Onyekaba MA, Mohamed AMT, Duncan K, Schirmer M, Walker RL, Mayassi T, Pierce KA, \u0026Aacute;vila-Pacheco J, Clish CB, Vlamakis H, Xavier RJ (2022) Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the intestine. Nat Microbiol 7:1673-1685.https://doi.org/10.1038/s41564-022-01224-7.\u003c/li\u003e\n\u003cli\u003eZhao J, Bai M, Ning X, Qin Y, Wang Y, Yu Z, Dong R, Zhang Y, Sun S (2022) Expansion of Escherichia-Shigella in Gut Is Associated with the Onset and Response to Immunosuppressive Therapy of IgA Nephropathy. J Am Soc Nephrol 33:2276-2292.https://doi.org/10.1681/ASN.2022020189.\u003c/li\u003e\n\u003cli\u003eMartin RM, Bachman MA (2018) Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front Cell Infect Microbiol 8:4.https://doi.org/10.3389/fcimb.2018.00004.\u003c/li\u003e\n\u003cli\u003eMishra A, Nam GH, Gim JA, Lee HE, Jo A, Kim HS (2018) Current Challenges of Streptococcus Infection and Effective Molecular, Cellular, and Environmental Control Methods in Aquaculture. Mol Cells 41:495-505.https://doi.org/10.14348/molcells.2018.2154.\u003c/li\u003e\n\u003cli\u003eLi H, Wang XK, Tang M, Lei L, Li JR, Sun H, Jiang J, Dong B, Li HY, Jiang JD, Peng ZG (2024) Bacteroides thetaiotaomicron ameliorates mouse hepatic steatosis through regulating gut microbial composition, gut-liver folate and unsaturated fatty acids metabolism. Gut Microbes 16:2304159.https://doi.org/10.1080/19490976.2024.2304159.\u003c/li\u003e\n\u003cli\u003eAhn JR, Lee SH, Kim B, Nam MH, Ahn YK, Park YM, Jeong SM, Park MJ, Song KB, Lee SY, Hong SJ (2022) Ruminococcus gnavus ameliorates atopic dermatitis by enhancing Treg cell and metabolites in BALB/c mice. Pediatr Allergy Immunol 33:e13678.https://doi.org/10.1111/pai.13678.\u003c/li\u003e\n\u003cli\u003eFlint HJ, Scott KP, Duncan SH, Louis P, Forano E (2012) Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3:289-306.https://doi.org/10.4161/gmic.19897.\u003c/li\u003e\n\u003cli\u003eYan Y, Lei Y, Qu Y, Fan Z, Zhang T, Xu Y, Du Q, Brugger D, Chen Y, Zhang K, Zhang E (2023) Bacteroides uniformis-induced perturbations in colonic microbiota and bile acid levels inhibit TH17 differentiation and ameliorate colitis developments. NPJ Biofilms Microbiomes 9:56.https://doi.org/10.1038/s41522-023-00420-5.\u003c/li\u003e\n\u003cli\u003eHeinken A, Khan MT, Paglia G, Rodionov DA, Harmsen HJ, Thiele I (2014) Functional metabolic map of Faecalibacterium prausnitzii, a beneficial human gut microbe. J Bacteriol 196:3289-3302.https://doi.org/10.1128/JB.01780-14.\u003c/li\u003e\n\u003cli\u003eHaas KN, Blanchard JL (2017) Kineothrix alysoides, gen. nov., sp. nov., a saccharolytic butyrate-producer within the family Lachnospiraceae. Int J Syst Evol Microbiol 67:402-410.https://doi.org/10.1099/ijsem.0.001643.\u003c/li\u003e\n\u003cli\u003eLiu D, Xie LS, Lian S, Li K, Yang Y, Wang WZ, Hu S, Liu SJ, Liu C, He Z (2024) Anaerostipes hadrus, a butyrate-producing bacterium capable of metabolizing 5-fluorouracil. mSphere 9:e0081623.https://doi.org/10.1128/msphere.00816-23.\u003c/li\u003e\n\u003cli\u003eSasaki M, Suaini NHA, Afghani J, Heye KN, O\u0026apos;Mahony L, Venter C, Lauener R, Frei R, Roduit C (2024) Systematic review of the association between short chain fatty acids and allergic diseases. Allergy.https://doi.org/10.1111/all.16065.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Preschool age, Allergic rhinitis, Functional constipation, Gut microbiota, Microbiota Function ","lastPublishedDoi":"10.21203/rs.3.rs-4493967/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4493967/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudies suggest that functional constipation (FC) is more common in preschool children with allergic rhinitis (AR) compared to those without. FC can significantly impact a child's quality of life. This study investigated the relationship between AR and FC in children diagnosed with both conditions (disease group) and a healthy control group. We compared the gut microbiota (GM) composition of children in both groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u003cstrong\u003e \u003c/strong\u003e16S rRNA sequencing technology was employed to compare the GMsequencing results of 32 children with AR and FC and 21 healthy children.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompared with the healthy group: 1) the GM α-diversity in the disease group was significantly higher (\u003cem\u003eP\u003c/em\u003e=0.014); 2) At the phylum level, the abundance of \u003cem\u003eBacteroidetes \u003c/em\u003e(P\u0026lt;0.05) decreased significantly, while that of \u003cem\u003eProteobateria\u003c/em\u003e was increased significantly in the disease group (P\u0026lt;0.05); 3) At the genus (species) level, the abundance of \u003cem\u003eBifidobacterium\u003c/em\u003e, \u003cem\u003ePhascolarctobacterium\u003c/em\u003e, \u003cem\u003eVeillonella \u003c/em\u003e(\u003cem\u003eVeillonella_parvula\u003c/em\u003e, \u003cem\u003eVeillonella_dispar\u003c/em\u003e), \u003cem\u003eEscherichia/Shigella\u003c/em\u003e, \u003cem\u003eKlebsiella \u003c/em\u003e(\u003cem\u003eKlebsiella_pneumoniae\u003c/em\u003e) \u003cem\u003e,Streptococcus, Escherichia/Shigella \u003c/em\u003eand \u003cem\u003eBacteroides_thetaiotaomicron \u003c/em\u003eincreased (P\u0026lt;0.05), but the abundance of \u003cem\u003eBacteroides \u003c/em\u003e(\u003cem\u003eBacteroides_uniformis\u003c/em\u003e)\u003cem\u003e, Faecalibacterium \u003c/em\u003e(\u003cem\u003eFaecalibacterium_prausnitzii\u003c/em\u003e)\u003cem\u003e, Ruminococcus, Kineothrix \u003c/em\u003e(\u003cem\u003eKineothrix_alysoides\u003c/em\u003e)\u003cem\u003e, Anaerostipes \u003c/em\u003e(\u003cem\u003eAnaerostipes_hadrus\u003c/em\u003e) and \u003cem\u003eBifidobacterium_longum \u003c/em\u003edecreased significantly in disease group (P\u0026lt;0.05). 4) The abundance of functional pathways related to carbohydrate metabolism, lipid metabolism, Transport_and_Catabolism, Endocrine_System, Nervous_System, Metabolic_Diseases and Immune_System were significantly decreased. 5) Furthermore, GM was found to be correlated with the clinical features of the disease group.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnalysis of the GM composition and function in the disease group suggests that supplementing the disease group with probiotics that produce butyric acid and dietary fiber (prebiotics) may correct dysregulation of GM, thereby improve AR and FC symptoms.\u003c/p\u003e","manuscriptTitle":"Gut microbiota composition and functional classification in preschool children with allergic rhinitis and functional constipation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-14 18:43:48","doi":"10.21203/rs.3.rs-4493967/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":"ab7311f3-b851-474f-abf2-2fdbd3a00e72","owner":[],"postedDate":"June 14th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":33134330,"name":"Biological sciences/Microbiology"},{"id":33134331,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2024-07-19T16:44:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-14 18:43:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4493967","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4493967","identity":"rs-4493967","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}