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.
Highlights
Bile acids (BAs) are synthesized from cholesterol, conjugated with taurine or glycine in liver, secreted into bile, and delivered to the intestine
We hypothesized that the increase of deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA) in serum of Organic anion transporting polypeptide 1a1 (Oatp1a1)-null mice is due to an increase in intestinal bacteria, and the purpose of the present study is to investigate the in vivo role of Oatp1a1 in BA metabolism and intestinal bacteria composition
DCA and TDCA, which are produced by intestinal bacteria, were increased in the serum of Oatp1a1-null mice [19]
Summary
Bile acids (BAs) are synthesized from cholesterol, conjugated with taurine or glycine in liver, secreted into bile, and delivered to the intestine. The majority of BAs are absorbed from the intestine and return to the liver, which together is known as the enterohepatic circulation of BAs [1,2]. Primary BAs, which are synthesized in liver include cholic acid (CA), chenodeoxycholic acid (CDCA), a-muricholic acid (aMCA), and bMCA. Secondary BAs are formed from primary BAs by bacterial enzymes in the intestine. The major secondary BAs in rodents are deoxycholic acid (DCA), lithocholic acid (LCA), and murideoxycholic acid (MDCA), which are the 7-dehydroxylation products of CA, CDCA, and a/bMCA, respectively. The bacterial metabolism of BAs as well as the structures and abbreviations of various BAs are shown as Fig. 1
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