{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:49:09Z","timestamp":1782276549227,"version":"3.54.5"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Sperm quality is a key contributing factor in infertility. This study aimed to investigate the causal relationship between gut microbiota genera and abnormal spermatozoa (defects in sperm count, motility, or morphology) and to evaluate potential mediating factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>Summary statistics for gut microbiota genera, abnormal spermatozoa, microbiota metabolic pathways, immune cell traits, and serum bioavailable testosterone (BioT) levels were extracted from publicly available GWAS databases. A fixed\u2010effects meta\u2010analysis was performed on gut microbiota genera from the MiBioGen and DMP cohorts, followed by two\u2010sample Mendelian randomization (MR) analysis to evaluate causal associations. To strengthen reliability, a triangulation framework incorporating MR analyses, HyPrColoc colocalization analysis, and Steiger directionality tests was employed. Mediation analysis focused on microbiota metabolic pathways, immune cell traits, and BioT levels as potential mediators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eight gut microbiota genera showed significant causal associations with abnormal spermatozoa: four risk genera (\n                      <jats:italic>Lachnospiraceae UCG001.id.11321, Coprococcus 1.id.11301, Barnesiella, Dorea<\/jats:italic>\n                      ) and four protective genera (\n                      <jats:italic>Clostridium sensu stricto 1.id.1873, Ruminiclostridium 6.id.11356<\/jats:italic>\n                      ,\n                      <jats:italic>Lachnospiraceae_noname, Veillonella<\/jats:italic>\n                      ). The triangulation framework validated these causal relationships. Although two genera affected BioT levels, formal mediation analysis did not confirm BioT, immune cells, or metabolic pathways as mediators, suggesting novel gut\u2010testis axis mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This large\u2010scale MR analysis establishes a causal connection between specific gut microbiota genera and abnormal spermatozoa. The \u201ccausation without colocalization\u201d pattern and null mediation findings suggest distant regulatory mechanisms and novel gut\u2010testis axes, offering microbiota\u2010targeted therapeutic strategies for male infertility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.70263","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:05:28Z","timestamp":1780056328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Effects of Gut Microbial Genera on Abnormal Spermatozoa Revealed Through Integrated Mendelian Randomization and Mediation Analysis"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-9834","authenticated-orcid":false,"given":"Huixiang","family":"Yang","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center The Fourth Affiliated Hospital of Jiangsu University  Zhenjiang Jiangsu 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