Enterobacteria-mediated deconjugation of taurocholic acid enhances ileal farnesoid X receptor signaling.

Hideaki Kuribayashi, Masaaki Miyata, Hiroki Yamakawa, Kouichi Yoshinari, Yasushi Yamazoe

Tohoku University, Graduate School of Pharmaceitical Sciences, Division of Drug Metabolism and Molecular Toxicology, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.

European journal of pharmacology 2012 Dec 15

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Enterobacteria are known to deconjugate amino acid-conjugated bile acids in the intestine. Administration of ampicillin (ABPC; 3 days, 100mg/kg) decreased the expression of ileal farnesoid X receptor (Fxr) target genes, and increased the levels of total bile acids in the intestinal lumen. The primary tauro-conjugates of cholic acid (TCA) and beta-muricholic acid (TβMCA) levels were increased, whereas the primary unconjugates, cholic acid (CA) and beta-muricholic acid (βMCA), levels decreased to below detectable levels (<0.01μmol) in ABPC-treated mice. The effects of individual bile acid on expression of the ileal farnesoid X receptor target genes were examined in ABPC-treated mice. The expression of ileal farnesoid X receptor target genes in ABPC-treated mice was clearly enhanced after CA (500mg/kg), but not TCA (500mg/kg) cotreatment. Their levels in control mice were enhanced after either CA or TCA-cotreatment. Unconjugated CA levels in the intestinal lumen and portal vein were increased in both ABPC-treated and control mice. Reduced ileal Fgf15 and Shp mRNA levels in ABPC-treated mice were also increased after CA (100mg/kg) cotreatment at which luminal CA levels was restored to the level in controls, but was unaffected by βMCA (100mg/kg) cotreatment. In addition, no increase in ileal Shp, Ibabp or Ostα mRNA levels was observed even after CA (500mg/kg) cotreatment in ABPC-treated farnesoid X receptor-null mice despite increased CA levels in the intestinal lumen. These results suggest the role of enterobacteria in bile acid-mediated enhancement of ileal farnesoid X receptor signaling by TCA deconjugation. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

Hideaki Kuribayashi, Masaaki Miyata, Hiroki Yamakawa, Kouichi Yoshinari, Yasushi Yamazoe. Enterobacteria-mediated deconjugation of taurocholic acid enhances ileal farnesoid X receptor signaling. European journal of pharmacology. 2012 Dec 15;697(1-3):132-8