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 i...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 chol-angiopathies 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 contro-versial 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.展开更多
基金This work was supported in part by the Dr.Nicholas C.High-tower Centennial Chair of Gastroenterology from Scott&White,a Veterans Health Administration Research Career Scientist award(IK6BX004601)a VA Merit award to Dr.G.Alpini(5I01BX000574)+1 种基金a VA Merit Award(1I01BX001724)to Dr.F.Meng from the United States Department of Veterans Affairs Biomedical Laboratory Researchthe USA National Institutes of Health(NIH)grants DK110035,DK054811,DK062975,DK115184,AA025997 and AA025157 to Drs.G.Alpini,F.Meng and S.Glaser.
文摘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 chol-angiopathies 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 contro-versial 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.
