{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T17:43:37Z","timestamp":1757612617327,"version":"3.44.0"},"reference-count":66,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The mediatory roles of immune cells in the gut microbiota and anovulation\u2010induced infertility remain unclear. This study aimed to investigate the correlations among gut microbiota, immunophenotypes, and anovulation\u2010induced female infertility using a mediation Mendelian randomization (MR) study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An MR design investigates the causal links among gut microbiota (<jats:italic>n<\/jats:italic> = 14\u00a0306, 195 bacterial taxa), 731 immunophenotypes, and anovulation\u2010induced female infertility (5667 anovulation\u2010induced infertile women and 117\u00a0098 controls). The causal effects were evaluated by MR Egger, weighted median, inverse variance weighted (IVW), simple mode method, and weighted mode.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two phylum members (Cyanobacteria and Bacteroidetes), an order member (Burkholderiales), a family member (Defluviitaleaceae), and seven genus members were causally correlated with the anovulation\u2010induced infertility. Among the seven genera, <jats:italic>Subdoligranulum<\/jats:italic>, <jats:italic>Clostridium innocuum<\/jats:italic> group, and <jats:italic>Escherichia.Shigella<\/jats:italic> were the risk factors, and <jats:italic>Prevotella9<\/jats:italic>, <jats:italic>Ruminococcus torques<\/jats:italic> group, <jats:italic>Eubacterium ventriosum<\/jats:italic> group, and <jats:italic>Eubacterium fissicatena<\/jats:italic> group were the protective factors in anovulation\u2010induced infertility. Next, 35 immunophenotypes were identified to be also causally correlated with the anovulation\u2010induced infertility. Among them, 15 immunophenotypes were significantly driven by the seven\u2010microbiota genus and might be the internal mediating mechanism of the influence of gut microbiota on anovulation\u2010induced female infertility. In the mediated MR analysis, four (<jats:italic>Clostridium innocuum<\/jats:italic> group, <jats:italic>Eubacterium fissicatena<\/jats:italic> group, <jats:italic>Eubacterium ventriosum<\/jats:italic> group, and <jats:italic>Prevotella9<\/jats:italic>) of the microbiota were directly influenced by six immunophenotypes (T cell, B cell, and dendritic cell panels) and then affected the anovulation\u2010induced infertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The mediation MR study provides evidence supporting immunophenotypes as mediators of gut microbiota\u2010influenced female infertility, especially anovulation\u2010induced infertility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70135","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T13:54:46Z","timestamp":1754920486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Immunophenotypes as a Mediator of Gut Microbiota\u2010Driven Female Anovulation\u2010Induced Infertility: A Mediation Mendelian Randomization Study"],"prefix":"10.1111","volume":"94","author":[{"given":"Xiyin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gynaecology and Obstetrics Gansu Second People's Hospital  Lanzhou Gansu China"},{"name":"Department of Gynaecology and Obstetrics The Affiliated Hospital of Northwest Minzu University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics Gansu Second People's Hospital  Lanzhou Gansu China"},{"name":"Department of Gynaecology and Obstetrics The Affiliated Hospital of Northwest Minzu University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyuan","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics Gansu Second People's Hospital  Lanzhou Gansu China"},{"name":"Department of Gynaecology and Obstetrics The Affiliated Hospital of Northwest Minzu University  Lanzhou Gansu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duozhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics Gansu Second People's Hospital  Lanzhou Gansu China"},{"name":"Department of Gynaecology and Obstetrics The Affiliated Hospital of Northwest Minzu University  Lanzhou Gansu 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