Increased intestinal permeability and bile acid accumulation via inhibition of the FXR-SHP pathway contribute to coumarin-induced systemic inflammation.

ABSTRACT: Coumarin causes severe poisoning in animals, affecting the development of agriculture and animal husbandry. Coumarin induces hepatotoxicity, but the inflammatory mechanism of coumarin is unclear. Here, we explored the effects of coumarin on systemic and hepatic inflammation. Our study found that coumarin reduced the abundance of Akkermansia muciniphila. The number of colonic goblet cells and the expression of Claudin 1 and ZO-1 were decreased in coumarin-treated groups, increasing intestinal permeability. Coumarin elevated the expression of lipopolysaccharide (LPS) biosynthesis genes and serum LPS. These changes increased oxidative stress indicators and total BA (TBA) in the liver. Coumarin inhibited Fxr and Shp expressions in the liver, thereby promoting

SUBMITTER: Shou N 

PROVIDER: S-EPMC12584623 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature