The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies

Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It associated with high rates of progression to end-stage liver disease as well a significant risk cholangiocarcinoma (CCA), gallbladder cancer, colorectal carcinoma. Currently, no effective medical treatment impact on the overall survival available, transplantation only curative option. Emerging evidence indicates that gut microbiota pathogenesis. Several studies analyzing fecal mucosal samples demonstrate distinct microbiome in individuals PSC compared healthy controls inflammatory bowel (IBD) without PSC. Experimental mouse observational human data suggest diverse set microbial functions may be relevant, including metabolites bacterial processing pharmacological agents, acids, or dietary compounds, altogether driving intrahepatic inflammation. Despite critical progress this field over past years, further functional characterization role related malignancies needed. In review, we discuss available elucidate important insights into underlying pathogenic mechanisms possible microbe-altering interventions.