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Vancomycin, a glycopeptide antibiotic, has emerged as a promising candidate. However, the mechanism by which vancomycin impacts the progression of PSC remains unknown. Mice treated with vancomycin exhibit increased hepatic collagen deposition and injury, due to the inhibition of intestinal FXR\u2010FGF15\/19 axis and the elevation of bile acid levels. These effects are associated with the reduction in <jats:italic>Clostridia XIVa<\/jats:italic>, especially <jats:italic>Clostridium scindens<\/jats:italic> (<jats:italic>C. scindens<\/jats:italic>). Gavage of <jats:italic>C. scindens<\/jats:italic> alleviates vancomycin\u2010induced bile acid accumulation and liver fibrosis via activating intestinal FXR\u2010FGF15\/19 signaling. Similar effects are observed in mice treated with engineered Escherichia coli Nissle 1917 that are capable of expressing bile acid 7\u03b1\u2010dehydratas (BaiE) from <jats:italic>C. scindens<\/jats:italic> (EcN\u2010BaiE). Activating intestinal FXR\u2010FGF15\/19 signaling by fexaramine (Fex) or recombinant protein FGF19 reverse vancomycin\u2010induced liver injury and fibrosis. These results demonstrate that long\u2010term oral vancomycin exacerbates cholestatic liver injury, while <jats:italic>C. scindens<\/jats:italic> mitigates this effect by activating the intestinal FXR\u2010FGF15\/19 signaling pathway. This underscores the importance of monitoring bile acid levels in PSC patients receiving vancomycin treatment and suggests that <jats:italic>C. scindens<\/jats:italic> may serve as a potential therapeutic approach for PSC patients.<\/jats:p>","DOI":"10.1002\/advs.202406445","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T14:44:32Z","timestamp":1734360272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<i>Clostridium Scindens<\/i> Protects Against Vancomycin\u2010Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR\u2010FGF15\/19 Signaling"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4072-7816","authenticated-orcid":false,"given":"Jintao","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Xiangya Hospital Central South University  Changsha Hunan 410008 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