{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:22:32Z","timestamp":1790605352217,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81674011"],"award-info":[{"award-number":["81674011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Currently, there is a variety of evidence linking the gut microbiota to changes in sex hormones. In contrast, the causal relationship between SHBG, a carrier of sex hormones, and the gut microbiota is unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>Bidirectional two\u2010sample Mendelian randomization (MR) analysis was used to detect the causal effect between SHBG and the gut microbiome. Summary statistics of genome\u2010wide association studies (GWASs) for the gut microbiome and SHBG were obtained from public datasets. Inverse\u2010variance weighting (IVW), weighted median, weighted mode, MR\u2010Egger and simple mode methods were used to operate the MR analysis. <jats:italic>F<\/jats:italic>\u2010statistics and sensitivity analyses performed to evaluate bias and reliability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When we set gut microbiome as exposure and SHBG as outcome, we identified nine causal relationships. In males, <jats:italic>Coprobacter<\/jats:italic> (PIVW\u00a0=\u00a02.01\u00a0\u00d7\u00a010<jats:sup>\u22126<\/jats:sup>), <jats:italic>Ruminococcus<\/jats:italic>2 (PIVW\u00a0=\u00a03.40\u00a0\u00d7\u00a010<jats:sup>\u22125<\/jats:sup>), <jats:italic>Barnesiella<\/jats:italic> (PIVW\u00a0=\u00a02.79\u00a0\u00d7\u00a010<jats:sup>\u22122<\/jats:sup>), <jats:italic>Actinobacteria<\/jats:italic> (PIVW\u00a0=\u00a03.25\u00a0\u00d7\u00a010<jats:sup>\u22122<\/jats:sup>) and <jats:italic>Eubacterium fissicatena<\/jats:italic> groups (PIVW\u00a0=\u00a03.64\u00a0\u00d7\u00a010<jats:sup>\u22122<\/jats:sup>) were associated with lower SHBG levels; <jats:italic>Alphaproteobacteria<\/jats:italic> (PIVW\u00a0=\u00a01.61\u00a0\u00d7\u00a010<jats:sup>\u22122<\/jats:sup>) is associated with higher SHBG levels. In females, <jats:italic>Lachnoclostridium<\/jats:italic> (PIVW\u00a0=\u00a09.75\u00a0\u00d7\u00a010<jats:sup>\u22123<\/jats:sup>) and <jats:italic>Defluviitaleaceae<\/jats:italic> UCG011 (PIVW\u00a0=\u00a03.67\u00a0\u00d7\u00a010<jats:sup>\u22122<\/jats:sup>) were associated with higher SHBG levels; <jats:italic>Victivallaceae<\/jats:italic> (PIVW\u00a0=\u00a02.23\u00a0\u00d7\u00a010<jats:sup>\u22122<\/jats:sup>) was associated with lower SHBG levels. According to the results of reverse MR analysis, three significant causal effect of SHBG was found on gut microbiota. In males, <jats:italic>Dorea<\/jats:italic> (PIVW\u00a0=\u00a04.17\u00a0\u00d7\u00a010<jats:sup>\u22122<\/jats:sup>) and <jats:italic>Clostridiales<\/jats:italic> (PIVW\u00a0=\u00a04.36\u00a0\u00d7\u00a010<jats:sup>\u22122<\/jats:sup>) were associated with higher SHBG levels. In females, <jats:italic>Lachnoclostridium<\/jats:italic> (PIVW\u00a0=\u00a07.44\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>) was associated with higherr SHBG levels. No signifcant heterogeneity of instrumental variables or horizontal pleiotropy was found in bidirectional two\u2010sample MR analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study may provide new insights into the causal relationship between the gut microbiome and sex hormone\u2010binding protein levels, as well as new treatment and prevention strategies for diseases such as abnormal changes in sex hormones.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13824","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T08:09:51Z","timestamp":1707984591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Causal relationship between\u00a0gut microbiome and\u00a0sex hormone\u2010binding globulin: A\u00a0bidirectional two\u2010sample Mendelian randomization 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