{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:45:58Z","timestamp":1784958358529,"version":"3.55.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"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. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The gut microbiota and plasma metabolites play important roles in the progression of drug-induced liver injury (DILI). We investigated the causal associations between the gut microbiota, plasma metabolome, and DILI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The summary data for gut microbiota (<jats:italic>n<\/jats:italic> = 18,340), plasma metabolome (<jats:italic>n<\/jats:italic> = 8,299), and DILI (<jats:italic>n<\/jats:italic> = 366,838) were obtained from the large genome-wide association studies. A two-sample Mendelian randomization was performed to explore the associations between the gut microbiota, plasma metabolome, and DILI. Additionally, a two-step Mendelian randomization was performed to explore the potential metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five taxa were causally associated with DILI, including <jats:italic>Oscillospira<\/jats:italic> [odds ratio (OR) = 2.257, 95% confidence interval (CI) = 1.110\u20134.590], <jats:italic>Blautia<\/jats:italic> (OR = 2.311, 95% CI = 1.010\u20135.288), <jats:italic>Roseburia<\/jats:italic> (OR = 2.869, 95% CI = 1.429\u20135.761), <jats:italic>Fusicatenibacter<\/jats:italic> (OR = 1.995, 95% CI = 1.024\u20133.890), and <jats:italic>Prevotella 7<\/jats:italic> (OR = 1.549, 95% CI = 1.065\u20132.253). Moreover, 53 metabolites were causally associated with DILI. After mediation analysis, four taxa were found to affect DILI through five mediation metabolites. N6-carbamoylthreonyladenosine mediated the effect of <jats:italic>Blautia<\/jats:italic> on DILI. Acetylcarnitine mediated the effect of <jats:italic>Fusicatenibacter<\/jats:italic> on DILI. In addition, 4-cholesten-3-one mediated the effect of <jats:italic>Prevotella 7<\/jats:italic> on DILI. Furthermore, 5,6-dihydrothymine levels and the salicylate-to-citrate ratio mediated the effect of <jats:italic>Oscillospira<\/jats:italic> on DILI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We found that the gut microbiota could affect DILI through plasma metabolites, which could serve as potential biomarkers for risk stratification and elucidate underlying mechanisms for further investigation of DILI.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1432049","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T05:12:17Z","timestamp":1721279537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Gut microbiota causally affects drug-induced liver injury via plasma metabolites: a Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Haoshuang","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10045","DOI":"10.1038\/s41598-023-35916-9","article-title":"Prophylactic consequences of sodium salicylate nanoparticles in cisplatin-mediated hepatotoxicity","volume":"13","author":"Alkhalaf","year":"2023","journal-title":"Sci. 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