{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:22:27Z","timestamp":1792290147153,"version":"4.4.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31771417"],"award-info":[{"award-number":["31771417"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We assessed genome-wide association study (GWAS) summary statistics for gut microbiota and six common ADs, namely, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes (T1D), and celiac disease (CeD), from published GWASs. Two-sample MR analyses were first performed to identify causal bacterial taxa for ADs in discovery samples. Significant bacterial taxa were further replicated in independent replication outcome samples. A series of sensitivity analyses was performed to validate the robustness of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Combining the results from the discovery and replication stages, we identified one causal bacterial genus, <jats:italic>Bifidobacterium<\/jats:italic>. A higher relative abundance of the <jats:italic>Bifidobacterium<\/jats:italic> genus was associated with a higher risk of T1D [odds ratio (OR): 1.605; 95% CI, 1.339\u20131.922; <jats:italic>P<jats:sub>FDR<\/jats:sub><\/jats:italic> = 4.19 \u00d7 10<jats:sup>\u22127<\/jats:sup>] and CeD (OR: 1.401; 95% CI, 1.139\u20131.722; <jats:italic>P<jats:sub>FDR<\/jats:sub><\/jats:italic> = 2.03 \u00d7 10<jats:sup>\u22123<\/jats:sup>), respectively. Further sensitivity analyses validated the robustness of the above associations. The results of reverse MR analysis showed no evidence of reverse causality from T1D and CeD to the <jats:italic>Bifidobacterium<\/jats:italic> genus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study implied a causal relationship between the <jats:italic>Bifidobacterium<\/jats:italic> genus and T1D and CeD, thus providing novel insights into the gut microbiota-mediated development mechanism of ADs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.746998","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T06:11:22Z","timestamp":1643004682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":259,"title":["Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization 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