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A two\u2010sample MR analysis was employed to investigate the bidirectional causal effects of gut microbiota and circulating cytokines on SS, and mediation analyses were applied to discover potential mediating gut microbiota and circulating cytokines. A series of sensitivity analyses were conducted to address heterogeneity and pleiotropy concerns.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifteen taxa were found to be causally associated with SS, and SS had a causal effect on 26 taxa. A bidirectional causal relationship was identified between\n                      <jats:italic>CAG\u2010269 sp001916065<\/jats:italic>\n                      and SS, and between\n                      <jats:italic>UBA7703<\/jats:italic>\n                      and SS. Genetically predicted levels of five circulating cytokines\u2014MIG, IL\u20105, IL\u20101RA, IL\u20102RA, and SCGF\u2010\u03b2\u2014were found to potentially affect SS, and genetically predicted SS was associated with increased levels of two circulating cytokines, IL\u20101\u03b2 and IL\u20105. A bidirectional causal relationship was identified between circulating IL\u20105 and SS. Mediation analyses further revealed that circulating cytokines do not mediate the gut microbiome's influence on SS, and conversely, the gut microbiome does not influence circulating cytokines to affect SS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides compelling evidence for causal effects of gut microbiome composition and circulating cytokines on SS risk. Further mediation analysis suggests that these biological factors may operate independently to influence SS development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcla.70136","type":"journal-article","created":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T07:15:16Z","timestamp":1765005316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Evidence Implicating Gut Microbiota and Circulating Cytokines in Sj\u00f6gren's Syndrome"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7536-906X","authenticated-orcid":false,"given":"Yuchen","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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