Characterization of Bile Acid homeostasis in Germ‐free Mice

Abstract

Gut bacteria metabolize primary bile acids (BAs) in bile, to form secondary BAs. Changes in gut bacteria will alter BA composition in the host. The purpose of this study was to characterize BA composition in mice lacking the normal complement of bacteria. BA concentrations in sera, livers, gallbladder bile, and ileal tissue of conventional (Conv) and germ‐free (GF) mice (3‐months old, n=5/group) were quantified using a UPLC‐MS‐MS method. The mRNA of BA synthetic enzymes in liver was quantified by bDNA assays. The GF mice have increased total BAs in liver (3‐fold), gallbladder (40‐fold), and ileum (4‐fold). Taurine (T)‐conjugated BAs increased in serum, gallbladder bile, and ilea of GF mice. T‐conjugated β‐muricholic acid (βMCA) was the predominant BA in livers of GF mice, whereas T‐cholic acid was the predominant BA in livers of Conv mice. The mRNA of enzymes belonging to the alternative pathway for the synthesis of βMCA namely, Cyp27a1 and Cyp7b1 were increased in GF mice liver. T‐UDCA, which is thought to be a secondary BA, was increased in liver (3‐fold), ileum (3‐fold) and gallbladder (35 fold) of GF mice, suggesting that UDCA may be a primary BA in mice. In summary, this study suggests: (1) GF mice favor the synthesis of βMCA in the liver; (2) BA concentrations are increased in livers, gallbladders, and ileal tissue of GF mice, and (3) UDCA appears to be a primary BA. (Supported by grants DK‐081461, ES‐019487 and ES‐009649)