Administration of ampicillin elevates hepatic primary bile acid synthesis through suppression of ileal FGF15 expression

Abstract

Administration of the antibacterial drug ampicillin (ABPC) significantly increased hepatic bile acid concentrations. In the present study, we investigated the mechanisms for the elevation of bile acid levels in ABPC‐treated mice. Hepatic microsomal cholesterol 7α‐hydroxylation was increased 2.0‐fold in ABPC‐treated mice despite higher bile acid levels in the liver and small intestinal lumen. A marked decrease in ileal fibroblast growth factor 15 (FGF15) mRNA level was observed (3% of vehicle‐treated mice) in ABPC‐treated mice. These phenomena were also observed in mice co‐treated with bacitracin/streptomycin/neomycin, which are barely absorbed from the intestine. Secondary bile acid, deoxycholic acid (DCA and tauroDCA) and unconjugated CA contents in the small intestinal lumen were reduced to below detection limits (<0.01 μmol). In ABPC‐treated mice, co‐treatment with tauroDCA reversed reductions in ileal FGF15 mRNA level. ABPC administration to farnesoid X receptor (Fxr)‐null mice also decreased ileal FGF15 mRNA levels. These results suggest that ABPC administration elevates hepatic primary bile acid synthesis, at least in part, through suppression of ileal FGF15 expression.