Abstract：
: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.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Kuribayashi H,Miyata M,Yamakawa H,Yoshinari K,Yamazoe Ydoi
10.1016/j.ejphar.2012.09.048subject
Has Abstractpub_date
2012-12-15 00:00:00pages
132-8issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(12)00822-9journal_volume
697pub_type
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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pub_type： 杂志文章
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