Activation of gut FXR improves the metabolism of bile acids, intestinal barrier, and microbiota under cholestatic condition caused by GCDCA in mice

Glycochenodeoxycholate (GCDCA) is a hydrophobic bile acid (BA) in humans and is highly increased in the serum and stool of liver fibrosis patients. However, the effects of GCDCA were not comprehensively investigated in the process of liver bile acid metabolism, gut microbiota, and intestinal barrier. It was reported that GCDCA can promote liver fibrosis via the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway in mice, and gut farnesoid X receptor activation alleviated the fibrosis caused by GCDCA in our previous study. Gut microbiota is also responsible for BA metabolism; meanwhile, BA metabolism may also exert an effect on the intestinal barrier. Nowadays, the comprehensive understanding of gut microbiota and intestinal barrier in relation to BA disorder was still insufficient. Current study further investigated the role of GCDCA in BA metabolism, gut microbiota, and intestinal barrier to help understand the effects of GCDCA in liver fibrosis, which may provide intervention methods for liver fibrosis caused by dysregulation of BA metabolism.