The gut microbiota regulates mouse biliary regenerative responses

Abstract

Injury to the biliary epithelium triggers cholangiopathies. However, factors involved in regulating the pathogenesis remains incompletely understood. Here, we report that the gut microbiota is important in regulating hepatobiliary fibroproliferative regenerative process. In helminth Clonorchis sinensis-induced bile duct injury model, wild-type mice showed more extensive peribiliary fibroproliferative responses than non-littermate IL-33-deficient mice. However, these reactions could be attenuated by co-housing of the animals together. In the meantime, the relatively fibroproliferative-resistant IL-33-deficient mice could become fibroproliferative-responsive especially in large intrahepatic bile duct by antibiotics treatment. Furthermore, microbiota-derived metabolite butyrate was able to inhibit biliary organoid expansion in vitro and temper 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced biliary fibrosis in vivo. Together, our data implies a potential way of management of hepatobiliary diseases by modulating gut microbiota.