Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr−/−) mouse model with hepato-biliary pathology

Abstract

BackgroundCftr−/−tm1Unc mice develop progressive hepato-biliary pathology. We hypothesize that this liver pathology is related to alterations in biliary bile hydrophobicity and bile salt metabolism in Cftr−/−tm1Unc mice. MethodsWe determined bile production, biliary and fecal bile salt- and lipid compositions and fecal bacterial composition of C57BL/6J Cftr−/−tm1Unc and control mice. ResultsWe found no differences between the total biliary bile salt or lipid concentrations of Cftr−/− and controls. Compared to controls, Cftr−/− mice had a ~30% higher bile production and a low bile hydrophobicity, related to a ~7 fold higher concentration of the choleretic and hydrophilic bile salt ursocholate. These findings coexisted with a significantly smaller quantity of fecal Bacteroides bacteria. ConclusionsLiver pathology in Cftr−/−tm1Unc is not related to increased bile hydrophobicity. Cftr−/− mice do however display a biliary phenotype characterized by increased bile production and decreased biliary hydrophobicity. Our findings suggest Cftr dependent, alterations in intestinal bacterial biotransformation of bile salts.