Epimerization of the four 3,7-dihydroxy bile acid epimers by human fecal microorganisms in anaerobic mixed cultures and in feces

The conversion of 3,7-dihydroxy bile acids by anaerobic mixed cultures of intestinal microorganisms was studied in fecal samples from eight healthy adult males. Incubations using substrate chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) were performed simultaneously in separate microbial suspensions from the same fecal samples. A time course study was done on four samples, chosen randomly from the eight. In the incubation of CDCA, substrate CDCA always decreased rapidly in amount; UDCA increased in amount, as did 3 beta, 7 beta-dihydroxy-5 beta-cholanoic acid (3 beta, 7 beta) and 3 beta, 7 alpha-dihydroxy-5 beta-cholanoic acid (3 beta, 7 alpha). In the incubation of UDCA, UDCA gradually decreased in amount; (3 beta, 7 beta), CDCA, and (3 beta, 7 alpha) increased gradually in amount. All reactions involved four epimers. After 48-72 hr UDCA was predominant and the reactions appeared to have reached equilibrium. In cultures from all eight samples, after 72-96 hr, a predominance of beta-hydroxy configurations at 7-position and alpha-hydroxy configurations at 3-position was observed. To compare these bile acid compositions to those in feces, an in vivo study using nine subjects was carried out. Concurrent with the collection of feces, transit time of food through the gut was measured. In samples from five subjects, in which amounts of lithocholic acid (LCA) was small, four 3,7-dihydroxy epimers were found. In samples from the other four, however, CDCA, the predominant epimer in bile, had apparently been converted to LCA by 7-dehydroxylation, and four epimers were not always found. In contrast to the incubation study, UDCA was not always the predominant 3,7-dihydroxy epimer in the fecal study. This may have been due to the transit times, which averaged 26.4 +/- 8.9 SD hr, being much shorter than the time it took for the incubation reactions to reach equilibrium.