Abnormalities in the gut microbiome in Mdr2−/− mice caused intestinal barrier dysfunction and increased bacterial translocation, which amplifies the hepatic nlrP3-mediated innate immune response.Transfer of the Mdr2−/− microbiota to healthy wildtype control mice induced significant liver damage in recipient mice.MDr2-associated cholestasis causes intestinal bacterial imbalance.Translocation of endotoxin into the portal vein and subsequent nlrP3 inflammasome activation contributes to higher liver damage. This evidence concerns the gene ABCB4 and cholestasis.