POLYDEOXYCHOLATE IN HUMAN AND HAMSTER FECES - A MAJOR PRODUCT OF CHOLATE METABOLISM

Fecal bile acid excretion is one of the two major routes by which chol esterol is eliminated from the body, fecal cholesterol being the other . During their enterohepatic circulation, bile acids are secreted into the duodenum, pass down the jejunum and into the ileum where more tha n 95% is reabsorbed by the gut. Bile acids that escape reabsorption in the small intestine are metabolized by microorganisms in the large in testine. The major routes of metabolism are reported to be deconjugati on, dehydroxylation, especially at the 7alpha-hydroxy position, and de hydrogenation of the hydroxyl moieties. There are also some reports th at saponifiable metabolites containing mostly deoxycholic acid form a major component of the bile acids found in human feces. We have identi fied a novel metabolite of cholic acid, 3alpha-hydroxy polydeoxycholat e, in both human and hamster feces that is the major constituent of th ese saponifiable metabolites. Furthermore, we have shown in hamsters t hat the animals that excreted more bile acid were excreting the additi onal bile acid as polydeoxycholate. As expected, there was a negative correlation between bile acid excretion in the feces and plasma choles terol concentrations in these animals. We speculate that polydeoxychol ate is formed in the lower gut of both humans and hamsters and that, b y its formation, bile acid will be sequestered in an insoluble form, t hus inhibiting its reabsorption by the gut. This process may help to r educe plasma cholesterol concentrations and coronary heart disease in humans.