Gut-Liver Axis, Microbiota, Bile Acids, and Immune Response in Pathogenesis of Primary Sclerosing Cholangitis: An Overview.

Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive bile duct inflammation and fibrosis. Its strong association with inflammatory bowel disease (IBD) highlights the possible role of the gut-liver axis in disease pathogenesis. Here, we review the mechanisms that may contribute to the disruption of the gut-liver axis, leading to liver injury and the development of PSC. In particular, disruption of the intestinal barrier allows microbial products to enter the portal circulation, stimulating hepatic immune cells and triggering biliary inflammation. Concurrently, gut-primed lymphocytes expressing mucosal homing receptors migrate aberrantly to the liver, where they may contribute to biliary epithelial cell injury. Dysbiosis, characterized by reduced microbial diversity and the expansion of bile-tolerant and pro-inflammatory taxa, amplifies this immune activation and disturbs gut-liver homeostasis. Moreover, bile acids act as signaling molecules, regulating metabolism and immune responses through receptors such as FXR and TGR5. Dysregulation of these pathways may promote cholestasis, inflammation, and fibrosis. By understanding these interactions, we may identify novel therapeutic targets for PSC.