Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples

Background-Deoxycholic acid (DCA), implicated in the pathogenesis of gall s tones and colorectal. cancer, is mainly formed by bacterial deconjugation ( cholylglycine hydrolase (CGH)) and 7 alpha -dehydroxylation (7 alpha -dehyd roxylase (7 alpha DH)) of conjugated cholic acid (CA) in the caecum/proxima l colon. Despite this, most previous studies of CGH and 7 alpha -DH have be en in faeces rather than in caecal contents. In bacteria, CA increases 7 al pha -DH activity by substrate-enzyme induction but little is known about CA concentrations or CA/7 alpha -DH induction in the human colon. Aims and methods-Therefore, in fresh " faeces ", and in caecal aspirates ob tained during colonoscopy from 20 patients, we: (i) compared the activities of CGH and 7a-DH, (ii) measured 7 alpha -DH in patients with " low " and " high " percentages of DCA in fasting serum (less than and greater than the median), (iii) studied CA concentrations in the right and left halves of t he colon, and examined the relationships between (iv) 7 alpha -DH activity and CA concentration in caecal samples (evidence of substrate-enzyme induct ion), and (v) 7 alpha -DH and per cent DCA in serum. Results-Although mean CGH activity in the proximal colon (18.3 (SEM 4.40) x 10(-2) U/mg protein) was comparable with that in " faeces " (16.0 (4.10) x 10(-2) U/mg protein), mean 7a-DH in the caecum. (8.54 (1.08) x 10(-4) U/mg protein) was higher (p <0.05) than that in the left colon (5.72 (0.85) x 1 0(-4) U/mg protein). At both sites, 7a-DH was significantly greater in the " high " than in the " low " serum DCA subgroups. CA concentrations in the right colon (0.94 (0.08) mu mol/ml) were higher than those in the left (0.0 9 (0.03) mu mol/ml; p <0.001) while in the caecum. (but not in the faeces) there was a weak (r=0.58) but significant (p <0.005) linear relationship be tween 7 alpha -DH and CA concentration. At both sites, 7 alpha -DH was line arly related (p <0.005) to per cent DCA in serum. Interpretation/summary-These results: (i) confirm that there are marked reg ional differences in bile acid metabolism between the right and left halves of the colon, (ii) suggest that caecal and faecal 7 alpha -DH influence pe r cent DCA in serum (and, by inference, in bile), and (iii) show that the s ubstrate CA induces the enzyme 7 alpha -DH in the caecum.