Taurochenodeoxycholic acid ameliorates liver fibrosis by regulating gut microbiota and bile acids via hippo-YAP pathway.

Cholestatic liver disease is characterized by gut microbiota dysbiosis and excessive toxic hepatic bile acid accumulation. Regulation of gut microbiota and suppression of bile acid synthesis are potential strategies for the treatment of cholestatic liver disease. Fetal liver bile acids demonstrate cytoprotective properties during hepatic development, prompting investigation into their therapeutic potential in extrahepatic biliary atresia (EHBA) rats. Comparing bile acid profiles, taurochenodeoxycholic acid (TCDCA) most effectively reduced hepatic bile acids and fibrosis, while altering gut microbiota and increasing Lactobacillus abundance. Additionally, TCDCA treatment significantly decreased liver Yes-associated protein (YAP) expression, thus suppressing ductular reaction during cholestatic liver fibrosis. These findings highlight that TCDCA might be a promising functional bile acid for treating liver fibrosis by modulating gut microbiota and the Hippo-YAP pathway.