Functional roles of gut bacteria imbalance in cholangiopathies

Abstract

Cholangiopathies are caused by bile duct damage or inflammation followed by cholestasis leading to liver fibrosis. Bile duct epithelial cells, cholangiocytes, are a primary target for cholangiopathies. Ductular reaction is often observed in cholangiopathies and the proliferation of cholangiocytes is associated with ductular reaction and liver fibrogenesis. Accumulating evidence suggests that patients with cholangiopathies have different gut bacterial profiles from healthy individuals, indicating the association between gut microbiota and cholangiopathies. Bile acids are produced by hepatocytes and modified by gut bacteria. Bile acids regulate cholangiocyte proliferation but effects vary depending on the type of bile acids. Recent studies suggest that therapies targeting gut bacteria, such as antibiotics administration and gut bacteria depletion or therapies using gut bacteria-associated bile acids, such as ursodeoxycholic acid (UDCA) administration, may be useful for treatments of cholangiopathies, although data are controversial depending on animal models or cohorts. This review summarizes current understandings of functional roles of gut bacterial imbalance and strategies for treatments of cholangiopathies targeting gut bacteria. Keywords: Cholangiopathies, Bile acids, Gut bacteria, Cholangiocytes, Cholestasis, Inflammation