Intestinal bile salt absorption in Atp8b1 deficient mice

Background/Aims Mutations in the ATP8B1 gene can cause Progressive Familial Intrahepatic Cholestasis type 1. We have previously reported that Atp8b1G308V/G308V mice, a model for PFIC1, have slightly, but significantly, higher baseline serum bile salt (BS) concentrations compared to wt mice. Upon BS feeding, serum BS concentrations strongly increased in Atp8b1-deficient mice. Despite these findings, we observed only mildly impaired canalicular BS transport. In the present report we tested the hypothesis that Atp8b1G308V/G308V mice hyperabsorb BS in the intestine during BS feeding. Methods Intestinal BS absorption was measured in intestinal perfusion and in intestinal explants. In addition, we measured BS concentrations in portal blood. Ileal expression of the Fxr-targets Asbt, Ilbp and Shp was assessed. Results In wt and Atp8b1G308V/G308V mice, intestinal taurocholate absorption is primarily mediated by the ileal bile salt transporter Asbt. Neither of the experimental systems revealed enhanced absorption of BS in Atp8b1G308V/G308V mice compared to wt mice. In line with these observations, we found no difference in the ileal protein expression of Asbt. Induction of Shp expression during BS feeding also demonstrated that Fxr signalling is intact in Atp8b1G308V/G308V mice. Conclusions The accumulation of BS in plasma of Atp8b1G308V/G308V mice during BS feeding is not caused by increased intestinal BS absorption.