{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:53:18Z","timestamp":1790787198822,"version":"4.1.0"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium\u2019s genome-wide association study (GWAS) and the GWAS Catalog\u2019s HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran\u2019s Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23\u20135.74, <jats:italic>p<\/jats:italic> =\u20090.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18\u20130.73, <jats:italic>p<\/jats:italic> =\u20090.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11\u20130.91, <jats:italic>p<\/jats:italic> =\u20090.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06\u20130.78, <jats:italic>p<\/jats:italic> =\u20090.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09\u20130.8, <jats:italic>p<\/jats:italic> =\u20090.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04\u20130.66, <jats:italic>p<\/jats:italic> =\u20090.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21\u20130.98, <jats:italic>p<\/jats:italic> =\u20090.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1\u20131.03, <jats:italic>p<\/jats:italic> =\u20090.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1366181","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T13:22:52Z","timestamp":1709817772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Association between gut microbiota and Hirschsprung disease: a bidirectional two-sample Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Wei","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baijun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghao","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1053\/j.gastro.2012.09.055","article-title":"The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice","volume":"144","author":"Alemi","year":"2013","journal-title":"Gastroenterology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.chom.2021.11.001","article-title":"Human gut bacterial metabolism drives Th17 activation and colitis","volume":"30","author":"Alexander","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3389\/fimmu.2020.00123","article-title":"Training the fetal immune system through maternal inflammation-a layered hygiene hypothesis","volume":"11","author":"Apostol","year":"2020","journal-title":"Front. Immunol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature12331","article-title":"Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota","volume":"500","author":"Atarashi","year":"2013","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.chom.2015.04.004","article-title":"Dynamics and stabilization of the human gut microbiome during the first year of life","volume":"17","author":"Backhed","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"G443","DOI":"10.1152\/ajpgi.00194.2001","article-title":"The proximal colonic motor response to rectal mechanical and chemical stimulation","volume":"282","author":"Bampton","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1136\/gut.27.5.534","article-title":"Hirschsprung's disease and idiopathic megacolon in adults and adolescents","volume":"27","author":"Barnes","year":"1986","journal-title":"Gut"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/978-3-031-46891-9_15","article-title":"Systemic inflammation as the health-related communication tool between the human host and gut microbiota in the framework of predictive","volume":"18","author":"Behzadi","year":"2024","journal-title":"Prevent Personal Med."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.1053\/j.gastro.2007.03.103","article-title":"High mucosal serotonin availability in neonatal guinea pig ileum is associated with low serotonin transporter expression","volume":"132","author":"Bian","year":"2007","journal-title":"Gastroenterology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1093\/ije\/dyu005","article-title":"Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome","volume":"43","author":"Burgess","year":"2014","journal-title":"Int. J. Epidemiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1097\/EDE.0000000000000559","article-title":"Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants","volume":"28","author":"Burgess","year":"2017","journal-title":"Epidemiology"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int. J. Epidemiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.jad.2022.08.012","article-title":"Gut microbiota and major depressive disorder: a bidirectional Mendelian randomization","volume":"316","author":"Chen","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1186\/s12933-023-02045-6","article-title":"Roles of gut microbiota in atrial fibrillation: insights from Mendelian randomization analysis and genetic data from over 430,000 cohort study participants","volume":"22","author":"Dai","year":"2023","journal-title":"Cardiovasc. Diabetol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s40168-020-00914-w","article-title":"Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity-and neurotransmission-related proteins in young recipients","volume":"8","author":"D'Amato","year":"2020","journal-title":"Microbiome."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"k601","DOI":"10.1136\/bmj.k601","article-title":"Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.jpeds.2005.01.044","article-title":"Diagnosis of Hirschsprung's disease: a prospective, comparative accuracy study of common tests","volume":"146","author":"De Lorijn","year":"2005","journal-title":"J. Pediatr."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"6458","DOI":"10.1073\/pnas.1720017115","article-title":"Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks","volume":"115","author":"De Vadder","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"528202","DOI":"10.3389\/fimmu.2020.528202","article-title":"Recent insights on the maternal microbiota: impact on pregnancy outcomes","volume":"11","author":"Di Simone","year":"2020","journal-title":"Front. Immunol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/s41431-017-0053-7","article-title":"Genome-wide association study of Hirschsprung disease detects a novel low-frequency variant at the RET locus","volume":"26","author":"Fadista","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s12916-023-02863-1","article-title":"Cross-talks between gut microbiota and tobacco smoking: a two-sample Mendelian randomization study","volume":"21","author":"Fan","year":"2023","journal-title":"BMC Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1101\/gr.264473.120","article-title":"Whole-genome analysis of noncoding genetic variations identifies multiscale regulatory element perturbations associated with Hirschsprung disease","volume":"30","author":"Fu","year":"2020","journal-title":"Genome Res."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e14186","DOI":"10.1111\/nmo.14186","article-title":"Luminal short-chain fatty acids and 5-HT acutely activate myenteric neurons in the mouse proximal colon","volume":"33","author":"Fung","year":"2021","journal-title":"Neurogastroenterol. Motil."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/nature12721","article-title":"Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells","volume":"504","author":"Furusawa","year":"2013","journal-title":"Nature"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1053\/j.sempedsurg.2004.10.019","article-title":"Developmental biology of the enteric nervous system: pathogenesis of Hirschsprung's disease and other congenital dysmotilities","volume":"13","author":"Gershon","year":"2004","journal-title":"Semin. Pediatr. Surg."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1101\/gr.236000.118","article-title":"Metagenomic analysis with strain-level resolution reveals fine-scale variation in the human pregnancy microbiome","volume":"28","author":"Goltsman","year":"2018","journal-title":"Genome Res."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3389\/fped.2015.00017","article-title":"The human neonatal gut microbiome: a brief review","volume":"3","author":"Gritz","year":"2015","journal-title":"Front. Pediatr."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13059-017-1174-6","article-title":"Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes","volume":"18","author":"Gui","year":"2017","journal-title":"Genome Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/nrgastro.2017.149","article-title":"Hirschsprung disease\u2014integrating basic science and clinical medicine to improve outcomes","volume":"15","author":"Heuckeroth","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1186\/s12885-023-11493-y","article-title":"Causal effect between gut microbiota and pancreatic cancer: a two-sample Mendelian randomization study","volume":"23","author":"Jiang","year":"2023","journal-title":"BMC Cancer"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"G260","DOI":"10.1152\/ajpgi.00056.2008","article-title":"Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants","volume":"295","author":"Kidd","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e1009698","DOI":"10.1371\/journal.pgen.1009698","article-title":"Size matters: large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development","volume":"17","author":"Kuil","year":"2021","journal-title":"PLoS Genet."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41588-020-00763-1","article-title":"Large-scale association analyses identify host factors influencing human gut microbiome composition","volume":"53","author":"Kurilshikov","year":"2021","journal-title":"Nat. Genet."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e21654","DOI":"10.1016\/j.heliyon.2023.e21654","article-title":"Causal effects of gut microbiota on scoliosis: a bidirectional two-sample mendelian randomization study","volume":"9","author":"Lai","year":"2023","journal-title":"Heliyon."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"646","DOI":"10.3390\/nu15214646","article-title":"Association of gut Microbiota with age-related macular degeneration and Glaucoma: a bidirectional Mendelian randomization study","volume":"15","author":"Li","year":"2023","journal-title":"Nutrients"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e0162079","DOI":"10.1371\/journal.pone.0163239","article-title":"Characterization of intestinal microbiomes of Hirschsprung's disease patients with or without enterocolitis using Illumina-MiSeq high-throughput sequencing","volume":"11","author":"Li","year":"2016","journal-title":"PLoS One"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"360","DOI":"10.3390\/nu15020360","article-title":"Causal effects of specific gut microbiota on chronic kidney diseases and renal function-a two-sample Mendelian randomization study","volume":"15","author":"Li","year":"2023","journal-title":"Nutrients"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"101210","DOI":"10.1016\/j.plipres.2022.101210","article-title":"Bile acids and their receptors in regulation of gut health and diseases","volume":"89","author":"Lin","year":"2023","journal-title":"Prog. Lipid Res."},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2023.10.009","article-title":"Assessment of bidirectional relationships between frailty and mental disorders: a bidirectional Mendelian randomization study","author":"Ma","year":"2023","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref42","year":""},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e0277621","DOI":"10.1128\/spectrum.02776-21","article-title":"Survival strategies and metabolic interactions between Ruminococcus gauvreauii and Ruminococcoides bili, isolated from human bile","volume":"10","author":"Molinero","year":"2022","journal-title":"Microbiol Spectr."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/s41572-023-00465-y","article-title":"Hirschsprung disease","volume":"9","author":"Montalva","year":"2023","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.semcdb.2017.01.006","article-title":"Enteric nervous system development: a crest cell's journey from neural tube to colon","volume":"66","author":"Nagy","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1097\/MPG.0000000000001999","article-title":"Intestinal microbiota in Hirschsprung disease","volume":"67","author":"Neuvonen","year":"2018","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1053\/j.gastro.2016.07.044","article-title":"The effect of microbiota and the immune system on the development and Organization of the Enteric Nervous System","volume":"151","author":"Obata","year":"2016","journal-title":"Gastroenterology"},{"key":"ref48","year":""},{"key":"ref49","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ydbio.2019.10.011","article-title":"The enteric nervous system undergoes significant chemical and synaptic maturation during adolescence in mice","volume":"458","author":"Parathan","year":"2020","journal-title":"Dev. Biol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1007\/s11605-022-05560-1","article-title":"Adult Hirschsprung's Disease","volume":"27","author":"Pemmada","year":"2023","journal-title":"J. Gastrointest. Surg."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"eadk1887","DOI":"10.1101\/2023.02.15.528712","article-title":"The maternal microbiome promotes placental development in mice","volume":"9","author":"Pronovost","year":"2023","journal-title":"Sci. Adv."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1111\/jcmm.13375","article-title":"Development of interstitial cells of Cajal in the human digestive tract as the result of reciprocal induction of mesenchymal and neural crest cells","volume":"22","author":"Radenkovic","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1096\/fj.14-259598","article-title":"Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells","volume":"29","author":"Reigstad","year":"2015","journal-title":"FASEB J."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1681\/ASN.2016010098","article-title":"Mendelian randomization as an approach to assess causality using observational data","volume":"27","author":"Sekula","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"D977","DOI":"10.1093\/nar\/gkac1010","article-title":"The NHGRI-EBI GWAS catalog: knowledgebase and deposition resource","volume":"51","author":"Sollis","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1053\/j.gastro.2010.01.053","article-title":"Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats","volume":"138","author":"Soret","year":"2010","journal-title":"Gastroenterology"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1053\/j.gastro.2020.07.018","article-title":"Glial cell-derived neurotrophic factor induces enteric neurogenesis and improves Colon structure and function in mouse models of Hirschsprung disease","volume":"159","author":"Soret","year":"2020","journal-title":"Gastroenterology"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-018-0617-x","article-title":"Temporal development of the gut microbiome in early childhood from the TEDDY study","volume":"562","author":"Stewart","year":"2018","journal-title":"Nature"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1080\/19490976.2019.1650997","article-title":"The association between gut microbiota development and maturation of intestinal bile acid metabolism in the first 3 y of healthy Japanese infants","volume":"11","author":"Tanaka","year":"2020","journal-title":"Gut Microbes"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"e111139","DOI":"10.15252\/embj.2022111139","article-title":"Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA-induced MEK1\/2 signaling pathway","volume":"42","author":"Tian","year":"2023","journal-title":"EMBO J."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e2211986120","DOI":"10.1073\/pnas.2211986120","article-title":"Ret deficiency decreases neural crest progenitor proliferation and restricts fate potential during enteric nervous system development","volume":"120","author":"Vincent","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"5813","DOI":"10.1038\/s41467-019-13721-1","article-title":"Relationship between gut microbiota and circulating metabolites in population-based cohorts","volume":"10","author":"Vojinovic","year":"2019","journal-title":"Nat. Commun."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12876-020-01195-1","article-title":"Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation","volume":"20","author":"Wang","year":"2020","journal-title":"BMC Gastroenterol."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1117905","DOI":"10.3389\/fmicb.2023.1117905","article-title":"Enteric nervous system damage caused by abnormal intestinal butyrate metabolism may lead to functional constipation","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"10075","DOI":"10.1021\/acs.jafc.3c02179","article-title":"Effects on diabetic mice of consuming lipid extracted from foxtail millet (Setaria italica): gut microbiota analysis and serum metabolomics","volume":"71","author":"Wang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1007\/BF02052222","article-title":"Hirschsprung's disease in adolescents and adults","volume":"33","author":"Wheatley","year":"1990","journal-title":"Dis. Colon Rectum"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"9105","DOI":"10.18632\/aging.205019","article-title":"Gut microbiota and hypertensive disorders in pregnancy: evidence from the Mendelian randomization study","volume":"15","author":"Wu","year":"2023","journal-title":"Aging"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"544","DOI":"10.3390\/nu15214544","article-title":"Causality investigation between gut microbiota, derived metabolites, and obstructive sleep apnea: a bidirectional Mendelian randomization study","volume":"15","author":"Yan","year":"2023","journal-title":"Nutrients"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.bbrc.2014.01.104","article-title":"Characterization of the intestinal microbiome of Hirschsprung's disease with and without enterocolitis","volume":"445","author":"Yan","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.cell.2015.02.047","article-title":"Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis","volume":"161","author":"Yano","year":"2015","journal-title":"Cell"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"343ra81","DOI":"10.1126\/scitranslmed.aad0917","article-title":"Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability","volume":"8","author":"Yassour","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"S0006-3223(23)01718-3","DOI":"10.1016\/j.biopsych.2023.11.006","article-title":"Brain-wide Mendelian randomization study of anxiety disorders and symptoms","author":"Zanoaga","year":"2023","journal-title":"Biol. Psychiatry"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1273104","DOI":"10.3389\/fnagi.2023.1273104","article-title":"Unraveling the connection between gut microbiota and Alzheimer's disease: a two-sample Mendelian randomization analysis","volume":"15","author":"Zeng","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"8295580","DOI":"10.1155\/2022\/8295580","article-title":"Electroacupuncture attenuated anxiety and depression-like behavior via inhibition of hippocampal inflammatory response and metabolic disorders in TNBS-induced IBD rats","volume":"2022","author":"Zhou","year":"2022","journal-title":"Oxid. Med. Cell. Longev."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1366181\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T13:22:55Z","timestamp":1709817775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1366181\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,7]]},"references-count":76,"alternative-id":["10.3389\/fmicb.2024.1366181"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1366181","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,7]]},"article-number":"1366181"}}