Abstract
In our study, ampicillin (AMP)-mediated decrease of enterobacteria caused increases in hepatic bile acid concentration through (at least in part) elevation of bile acid synthesis in C57BL/6N mice. We investigated the involvement of enterobacteria on intestinal bile acid absorption in AMP-treated mice in the present study. Fecal enterobacterial levels and fecal bile acid excretion rates were markedly decreased in mice treated with AMP (100 mg/kg) for 3 days, whereas bile acid concentrations in portal blood were significantly increased compared with those in mice treated with a vehicle. Ileal apical sodium-dependent bile acid transporter (SLC10A2) mRNA levels and ileal SLC10A2 protein levels in brush-border membranes were significantly increased compared with those in mice treated with the vehicle. In AMP-treated mice, total bile acid levels were increased, whereas levels of enterobacteria-biotransformed bile acid, taurodeoxycholic acid, and cholic acid were decreased in intestinal lumen. These phenomena were also observed in farnesoid X receptor-null mice treated with AMP for 3 days. Discontinuation of AMP administration after 3 days (vehicle administration for 4 days) increased levels of fecal enterobacteria, fecal bile acid excretion, and taurodeoxycholic acid and cholic acid in the intestinal lumen, whereas the discontinuation decreased ileal SLC10A2 expression and bile acid concentrations in the portal blood. Coadministration of taurodeoxycholic acid or cholic acid decreased ileal SLC10A2 expression in mice treated with AMP. These results suggest that enterobacteria-mediated bile acid biotransformation modulates intestinal bile acid transport and homeostasis through down-regulation of ileal SLC10A2 expression.
Footnotes
This study was supported by the Ministry of Education, Culture, Sports Science, and Technology of Japan [Grants 21390039, 20590137] and the Yakult Bio-Science Foundation.
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.171736.
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ABBREVIATIONS:
- DCA
- deoxycholic acid
- AMP
- ampicillin
- ASBT
- apical sodium-dependent bile acid transporter
- SHP
- small heterodimer partner
- FGF
- fibroblast growth factor
- FXR
- farnesoid X receptor
- LCA
- lithocholic acid
- TDCA
- taurodeoxycholic acid
- TβMCA
- tauro-β-muricholic acid
- CA
- cholic acid
- TCA
- taurocholic acid
- TCDCA
- taurochenodeoxycholic acid
- IBABP
- ileal bile acid binding protein
- OSTα/β
- organic solute transporter α/β
- BBM
- brush border membrane
- qPCR
- quantitative polymerase chain reaction
- HPLC
- high-performance liquid chromatography.
- Received June 22, 2010.
- Accepted September 29, 2010.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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