{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:51:16Z","timestamp":1788274276705,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"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>The gut microbiota (GM) plays a pivotal role in influencing various health outcomes, including immune-mediated conditions, but its potential association with autoimmune thyroid disease (AITD) remains underexplored. We aimed to investigate the potentially pathogenic or protective causal impacts of specific GM on two types of AITD, namely Graves\u2019 disease and Hashimoto\u2019s thyroiditis, and analyzed the mediating effect of 731 immune cell phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Leveraging pooled genome-wide association study (GWAS) data of 211 gut microbiota traits, 731 immune cell phenotypes, and two types of AITD (Hashimoto\u2019s thyroiditis and Graves\u2019 disease), we performed bidirectional Mendelian randomization (MR) analyses to explore the causal relationships between the GM and AITD. Subsequently, we employed a multivariable MR analysis to discover potential mediating immune cell traits. Additionally, sensitivity analyses were utilized to ensure the reliability of the outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analysis revealed that a total of 7 GM taxa were positively associated with AITD, and other 14 taxa showed a negative correlation with AITD. Furthermore, we identified several immune cell traits that mediated the effects of GM on AITD. Most notably, <jats:italic>Actinobacteria (p)<\/jats:italic> presented protective effects on Hashimoto\u2019s thyroiditis via CCR2 on myeloid Dendritic Cell (5.0%), and <jats:italic>Bifidobacterium (g)<\/jats:italic> showed facilitating effects on Graves\u2019 disease through CD39+ CD4+ T cell %CD4+ T cell (5.0%) and CD14 on CD33+ HLA DR+ CD14dim (12.2%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The current MR study provides evidence supporting the causal relationships between several specific GM taxa and AITD, and further identified potential mediating immunophenotypes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1443643","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T04:44:22Z","timestamp":1726461862000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Gut microbiota and autoimmune thyroid disease: a bidirectional Mendelian randomization study and mediation analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Yiqiao","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaye","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.autrev.2014.10.016","article-title":"Autoimmune thyroid disorders","volume":"14","author":"Antonelli","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1111\/j.1523-5378.2010.00802.x","article-title":"Identification of a correlation between Helicobacter pylori infection and Graves' disease","volume":"15","author":"Bassi","year":"2010","journal-title":"Helicobacter"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.dld.2018.02.012","article-title":"Actinobacteria: a relevant minority for the maintenance of gut homeostasis","volume":"50","author":"Binda","year":"2018","journal-title":"Dig. Liver Dis."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.medmal.2013.10.002","article-title":"Probiotics, gut microbiota and health","volume":"44","author":"Butel","year":"2014","journal-title":"Med. Mal. 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Med."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.3389\/fimmu.2018.01197","article-title":"Cytokine secretion and Pyroptosis of thyroid follicular cells mediated by enhanced NLRP3, NLRP1, NLRC4, and AIM2 Inflammasomes are associated with autoimmune thyroiditis","volume":"9","author":"Guo","year":"2018","journal-title":"Front. Immunol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1128\/mBio.01492-17","article-title":"Dysbiosis and its discontents","volume":"8","author":"Hooks","year":"2017","journal-title":"mBio"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"811","DOI":"10.3389\/fendo.2018.00811","article-title":"Variations in CD14 gene are associated with autoimmune thyroid diseases in the Chinese population","volume":"9","author":"Jia","year":"2018","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"101373","DOI":"10.1016\/j.beem.2019.101373","article-title":"Thyro-entero-gastric autoimmunity: pathophysiology and implications for patient management","volume":"34","author":"Lahner","year":"2020","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1210\/jc.2005-1272","article-title":"Helicobacter pylori infection and autoimmune thyroid disease in young patients: the disadvantage of carrying the human leukocyte antigen-DRB1*0301 allele","volume":"91","author":"Larizza","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.jaut.2015.07.009","article-title":"Immunogenetics of autoimmune thyroid diseases: a comprehensive review","volume":"64","author":"Lee","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1186\/s12916-022-02657-x","article-title":"Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study","volume":"20","author":"Li","year":"2022","journal-title":"BMC Med."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"5036959","DOI":"10.1155\/2020\/5036959","article-title":"The composition of gut microbiota in patients bearing Hashimoto's thyroiditis with Euthyroidism and hypothyroidism","volume":"2020","author":"Liu","year":"2020","journal-title":"Int. J. Endocrinol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1267383","DOI":"10.3389\/fendo.2023.1267383","article-title":"Complex relationship between gut microbiota and thyroid dysfunction: a bidirectional two-sample Mendelian randomization study","volume":"14","author":"Liu","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1056\/NEJMra1600266","article-title":"The human intestinal microbiome in health and disease","volume":"375","author":"Lynch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/ni0111-5","article-title":"Diet, gut microbiota and immune responses","volume":"12","author":"Maslowski","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"813204","DOI":"10.3389\/fmed.2022.813204","article-title":"Guts imbalance imbalances the brain: a review of gut microbiota association with neurological and psychiatric disorders","volume":"9","author":"Mitrea","year":"2022","journal-title":"Front. Med."},{"key":"ref20","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":"ref21","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1001\/jama.2021.18236","article-title":"Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: the STROBE-MR statement","volume":"326","author":"Skrivankova","year":"2021","journal-title":"JAMA"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1046\/j.1365-2249.2003.02139.x","article-title":"Increased prevalence of antibodies to enteropathogenic Yersinia enterocolitica virulence proteins in relatives of patients with autoimmune thyroid disease","volume":"132","author":"Strieder","year":"2003","journal-title":"Clin. Exp. Immunol."},{"key":"ref23","first-page":"265","article-title":"Dysmicrobism, inflammatory bowel disease and thyroiditis: analysis of the literature","volume":"29","author":"Tomasello","year":"2015","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"k2179","DOI":"10.1136\/bmj.k2179","article-title":"Role of the gut microbiota in nutrition and health","volume":"361","author":"Valdes","year":"2018","journal-title":"BMJ"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"918","DOI":"10.3390\/cells12060918","article-title":"Molecular mechanisms in autoimmune thyroid disease","volume":"12","author":"Vargas-Uricoechea","year":"2023","journal-title":"Cells"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s11154-018-9467-y","article-title":"Gut microbiota and Hashimoto's thyroiditis","volume":"19","author":"Virili","year":"2018","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.cytogfr.2019.06.003","article-title":"CD14: biology and role in the pathogenesis of disease","volume":"48","author":"Wu","year":"2019","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1240752","DOI":"10.3389\/fendo.2023.1240752","article-title":"Relationship between gut microbiota and thyroid function: a two-sample Mendelian randomization study","volume":"14","author":"Xie","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1186\/s12916-023-02878-8","article-title":"Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn's disease: a multi-omics Mendelian randomization study","volume":"21","author":"Xu","year":"2023","journal-title":"BMC Med."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"746998","DOI":"10.3389\/fimmu.2021.746998","article-title":"Causal relationship between gut microbiota and autoimmune diseases: a two-sample Mendelian randomization study","volume":"12","author":"Xu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1038\/s41467-017-01917-2","article-title":"Remodelling of the gut microbiota by hyperactive NLRP3 induces regulatory T cells to maintain homeostasis","volume":"8","author":"Yao","year":"2017","journal-title":"Nat. Commun."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1089\/thy.2017.0395","article-title":"Alterations of the gut microbiota in Hashimoto's thyroiditis patients","volume":"28","author":"Zhao","year":"2018","journal-title":"Thyroid"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between microbiota and immunity in health and disease","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1443643\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T04:44:24Z","timestamp":1726461864000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1443643\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,16]]},"references-count":33,"alternative-id":["10.3389\/fmicb.2024.1443643"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1443643","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,16]]},"article-number":"1443643"}}