Dysfunction of organic anion transporting polypeptide 1a1 alters intestinal bacteria and bile acid metabolism in mice

PLoS One. 2012;7(4):e34522. doi: 10.1371/journal.pone.0034522. Epub 2012 Apr 4.

Abstract

Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in liver and is able to transport bile acids (BAs) in vitro. Male Oatp1a1-null mice have increased concentrations of taurodeoxycholic acid (TDCA), a secondary BA generated by intestinal bacteria, in both serum and livers. Therefore, in the present study, BA concentrations and intestinal bacteria in wild-type (WT) and Oatp1a1-null mice were quantified to investigate whether the increase of secondary BAs in Oatp1a1-null mice is due to alterations in intestinal bacteria. The data demonstrate that Oatp1a1-null mice : (1) have similar bile flow and BA concentrations in bile as WT mice; (2) have a markedly different BA composition in the intestinal contents, with a decrease in conjugated BAs and an increase in unconjugated BAs; (3) have BAs in the feces that are more deconjugated, desulfated, 7-dehydroxylated, 3-epimerized, and oxidized, but less 7-epimerized; (4) have 10-fold more bacteria in the small intestine, and 2-fold more bacteria in the large intestine which is majorly due to a 200% increase in Bacteroides and a 30% reduction in Firmicutes; and (5) have a different urinary excretion of bacteria-related metabolites than WT mice. In conclusion, the present study for the first time established that lack of a liver transporter (Oatp1a1) markedly alters the intestinal environment in mice, namely the bacteria composition.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteria / genetics
  • Bacteria / growth & development*
  • Bacteria / metabolism
  • Bile Acids and Salts / metabolism*
  • DNA, Bacterial / genetics
  • DNA, Ribosomal / genetics
  • Feces / microbiology
  • Intestinal Mucosa / metabolism
  • Intestines / microbiology*
  • Intestines / pathology*
  • Liver / cytology
  • Liver / metabolism
  • Male
  • Metabolome
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organic Cation Transport Proteins / physiology*
  • Polymerase Chain Reaction

Substances

  • Bile Acids and Salts
  • DNA, Bacterial
  • DNA, Ribosomal
  • Oatp1a1 protein, mouse
  • Organic Cation Transport Proteins