Gut Microbiota in Primary Sclerosing Cholangitis: From Prognostic Role to Therapeutic Implications

Abstract

<b><i>Background:</i></b> Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of unknown etiology characterized by biliary inflammation and periductal fibrosis. The gut microbiota plays a crucial role in the pathogenesis of PSC by regulating bile acid metabolism, inflammation, and immune response. On the other hand, liver disease progression affects the composition of the gut microbiota, fostering these mechanisms in a mutual detrimental way. <b><i>Summary:</i></b> Recent evidences described a specific pro-inflammatory microbial signature in PSC patients, with an overall reduced bacterial diversity and the loss of beneficial metabolites such as short-chain fatty acids. As effective therapies for PSC are still lacking, targeting the gut microbiota offers a new perspective in the management of this disease. To date, antibiotics, fecal microbiota transplantation, and probiotics are the most studied gut microbiota-targeted intervention in PSC, but new potential strategies such as vaccines and bacteriophages represent possible future therapeutic horizons. <b><i>Key Messages:</i></b> In this review, we focus on the role of the gut microbiota in PSC, considering its pathogenetic and prognostic role and the therapeutic implications.