Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 697, Issue 1-3, Pages 132-138Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2012.09.048
Keywords
Bile acid; Enterobacteria; Deconjugation; Antibiotics; Farnesoid X receptor (Fxr)
Categories
Funding
- Ministry of Education, Culture, Sports Science, and Technology of Japan [21390039]
- Mishima Kaiun Memorial Foundation
- Grants-in-Aid for Scientific Research [24659064, 21390039] Funding Source: KAKEN
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Enterobacteria are known to deconjugate amino acid-conjugated bile acids in the intestine. Administration of ampicillin (ABPC; 3 days, 100 mg/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 (T beta MCA) levels were increased, whereas the primary unconjugates, cholic acid (CA) and beta-muricholic acid (beta MCA), levels decreased to below detectable levels (< 0.01 mu mol) 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 (500 mg/kg), but not TCA (500 mg/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 (100 mg/kg) cotreatment at which luminal CA levels was restored to the level in controls, but was unaffected by beta MCA (100 mg/kg) cotreatment. In addition, no increase in ileal Shp, Ibabp or Ost alpha mRNA levels was observed even after CA (500 mg/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. (C) 2012 Elsevier B.V. All rights reserved.
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