Colonic bacterial activity, biliary cholesterol saturation, and pathogenesis of gallstones

The relation between colonic bacterial metabolites in bile and saturation of bile with cholesterol was investigated. Eleven healthy men ingested metronidazole (2 g daily) for 10 days to inhibit anaerobic bacterial activity. Bile composition was determined in fasting samples aspirated from the duodenum before metronidazole was given, at the end of 10 days on metronidazole, and a month after the drug was discontinued. Bile cholesterol saturation fell in ten of the eleven subjects from a mean of 1.00 to 0.83 and rose in all eleven after the drug was stopped. At the same time the proportion of deoxycholate in bile acid decreased from a mean of 24% to 7%, returning to 22% of the total a month after metronidazole had been stopped, and the proportion of chenodeoxycholate changed significantly from 33% to 46% and back to 33%. There was little change in cholate concentrations. Deoxycholate is formed exclusively by bacterial action in the colon. Its administration increases cholesterol saturation of bile, while chenodeoxycholate reduces it. These results suggest that colonic function is important in regulating bile composition. Dietary measures which reduce the return of newly formed deoxycholate from the colon to the bile reduce cholesterol saturation and so are likely to reduce the risk of gallstones.