Alteration of Bile Acid Metabolism by Cimetidine in Healthy Humans

Abstract

Background

To clarify an effect of cimetidine on bile acid metabolism, we evaluated whether an increased deconjugation of bile acids would occur in healthy humans who have received cimetidine. We examined: 1) whether healthy volunteers taking cimetidine would have positive bile acid breath tests because of bacterial overgrowth in the jejunum; 2) whether the isolated bacteria would exhibit deconjugation ability; and 3) whether a change in gastric pH was related to the bacterial overgrowth.

Methods

We evaluated 73 healthy Japanese volunteers; 53 of them received cimetidine and 20 did not. Deconjugation of bile acids was detected as ¹⁴CO₂ specific activity of expired air measured by a bile acid breath test giving 5 μCi of oral glycine-1-¹⁴C labeled glycocholate. Aspiration of jejunal fluids was performed by a double lumen tube with a rubber cover on the tip, and deconjugation ability of bacteria was evaluated using thin layer chromatography.

Results

Samples of expired breath from the 53 healthy volunteers showed a significant increase in ¹⁴CO₂ specific activity after the administration of cimetidine rather than before the administration of cimetidine. Bacterial overgrowth was found in the jejunal fluid after the administration of cimetidine. The administration of tetracycline to 27 subjects significantly reduced the ¹⁴CO₂ specific activity. The following species were identified in the jejunal fluid samples obtained from the subjects: enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, B uniformis, Eubacterium lentum, E parvum, and Escherichia coli. Except for E coli, all of the bacterial species identified deconjugated bile acids. We observed a significant relationship between ¹⁴CO₂'s specific activity and gastric pH before and after administration of cimetidine, respectively.

Conclusions

Healthy volunteers who received cimetidine showed an increased deconjugation of bile acid caused by overgrowth of bacteria in the jejunum, which can deconjugate bile acids. The bacterial overgrowth is probably associated with a shift to neutral pH in the gastric juice caused by cimetidine.