{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:19:28Z","timestamp":1777997968993,"version":"3.51.4"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Despite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship between them remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gut microbiota data were obtained from the MiBioGen collaboration, and SpA genome-wide association study (GWAS) summary data were obtained from the FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, and weighted mode). Pleiotropy and heterogeneity were also assessed. Reverse MR analysis was used to detect reverse causal relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 23 causal links between specific gut microbiota taxa and SpA levels. Of these, 22 displayed nominal causal associations, and only one demonstrated a robust causal connection. Actinobacteria id.419 increased the risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29\u20132.69); <jats:italic>p<\/jats:italic> = 8.63<jats:italic>E<\/jats:italic>\u221204). The family Rikenellaceae id.967 was associated with a reduced risk of both AS (OR = 0.66 (95% CI: 0.47\u20130.93); <jats:italic>p<\/jats:italic> = 1.81<jats:italic>E<\/jats:italic>\u221202) and psoriatic arthritis (OR = 0.70 (95% CI: 0.50\u20130.97); <jats:italic>p<\/jats:italic> = 3.00<jats:italic>E<\/jats:italic>\u221202). Bacillales id.1674 increased the risk of AS (OR = 1.23 (95% CI: 1.00\u20131.51); <jats:italic>p<\/jats:italic> = 4.94<jats:italic>E<\/jats:italic>\u221202) and decreased the risk of enteropathic arthritis (OR = 0.56 (95% CI: 0.35\u20130.88); <jats:italic>p<\/jats:italic> = 1.14<jats:italic>E<\/jats:italic>\u221202). Directional pleiotropy, or heterogeneity, was not observed. No reverse causal associations were observed between the diseases and the gut microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our MR analysis suggested a genetic-level causal relationship between specific gut microbiota and SpA, providing insights into the underlying mechanisms behind SpA development mediated by gut microbiota.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1284466","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T15:20:07Z","timestamp":1707405607000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Causal association of gut microbiota on spondyloarthritis and its subtypes: a Mendelian randomization 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