Epimerization versus dehydroxylation of the 7 alpha-hydroxyl- group of primary bile acids: competitive studies with Clostridium absonum and 7 alpha-dehydroxylating bacteria (Eubacterium sp.).

Primary bile acids, chenodeoxycholic (3 alpha,7 alpha-dihydroxy-5 beta-cholan-24-oic) and cholic (3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholan-24-oic) were included in cultures of (a) Clostridium absonum alone (b) a mixture of C. absonum and a 7-dehydroxylating organism, Eubacterium sp. (c) a mixture of C. absonum and fecal bacteria, and (d) fecal bacteria alone. C. absonum, when added to Eubacterium sp. cultures totally prevented lithocholic acid formation when the substrate was chenodeoxycholic acid and halved deoxycholic acid formation when the substrate was cholic acid. As expected, formation of 7 beta-hydroxy- and 7-keto-bile acids took precedence over formation of 7 alpha-dehydroxylated bile acids. However, the addition of C. absonum to mixed fecal cultures containing chenodeoxycholic acid did not alter production of lithocholic (3 alpha-hydroxy-5 beta-cholan-24-oic) acid; instead it enhanced formation of ursodeoxycholic acid (3 alpha,7 beta-dihydroxy-5 beta-cholan-24-oic acid) at the expense of 7-keto-lithocholic acid (3 alpha-hydroxyl-7-oxo-5 beta-cholan-24-oic acid). Similarly, the addition of C. absonum to mixed fecal cultures containing cholic acid promoted production of ursocholic acid (3 alpha,7 beta,12 alpha-trihydroxy-5 beta-cholan-24-oic acid) which did not take place when C. absonum was not added. Surprisingly, deoxycholic acid formation was somewhat enhanced when C. absonum was added to fecal cultures. These studies suggest that successful introduction of "foreign" 7 alpha-epimerizing organisms into animal or human intestines may influence bile acid metabolism in vivo.