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The narrow therapeutic window causes COL to induce gastrointestinal adverse effects even when taken at recommended doses, mainly manifested as nausea, vomiting, and diarrhea. However, the mechanism of COL\u2010induced gastrointestinal toxic reactions remains obscure. In the present study, the mice were dosed with COL (2.5\u00a0mg\/kg b.w.\/day) for a week to explore the effect of COL on bile acid metabolism and the mechanism of COL\u2010induced diarrhea. The results showed that COL treatment affected liver biochemistry in mice, resulting in a significant down\u2010regulation of the mRNA expression levels of bile acid biosynthesis regulators <jats:italic>Cyp7a1<\/jats:italic>, <jats:italic>Cyp8b1<\/jats:italic>, <jats:italic>Cyp7b1<\/jats:italic>, and <jats:italic>Cyp27a1<\/jats:italic> in liver tissues. The mRNA expression levels of bile acid transporters <jats:italic>Ntcp<\/jats:italic>, <jats:italic>Oatp1<\/jats:italic>, <jats:italic>Mrp2<\/jats:italic>, <jats:italic>Ibabp<\/jats:italic>, <jats:italic>Mrp3<\/jats:italic>, <jats:italic>Osta<\/jats:italic>, and <jats:italic>Ostb<\/jats:italic> in liver and ileum tissues were also significantly down\u2010regulated. In addition, COL treatment significantly inhibited the mRNA expression levels of <jats:italic>Fxr<\/jats:italic> and its downstream target genes <jats:italic>Shp<\/jats:italic>, <jats:italic>Lrh1<\/jats:italic>, and <jats:italic>Fgf1<\/jats:italic>5 in liver and ileum tissues, affecting the feedback regulation of bile acid biosynthesis. More importantly, the inhibition of COL on bile acid transporters in ileal and hepatic tissues affected bile acid recycling in the ileum as well as their reuptake in the liver, leading to a significantly increased accumulation of bile acids in the colon, which may be an important cause of diarrhea. In conclusion, our study revealed that COL treatment affected bile acid biosynthesis and enterohepatic circulation, thereby disrupting bile acid metabolic homeostasis in mice.<\/jats:p>","DOI":"10.1002\/jat.4587","type":"journal-article","created":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T21:39:55Z","timestamp":1707082795000},"page":"863-873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Colchicine disrupts bile acid metabolic homeostasis by affecting the enterohepatic circulation in mice"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4574-3222","authenticated-orcid":false,"given":"Yongpeng","family":"Shi","sequence":"first","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wei","sequence":"additional","affiliation":[{"name":"Gansu Provincial Clinical 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