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

doi:10.1136/gut.49.6.835

Gut 2001;49:835-842; doi:10.1136/gut.49.6.835

Gut 2001;49:835-842 ( December )

Article

Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples L A Thomas^a, M J Veysey^a, G French^b, P B Hylemon^c, G M Murphy^a, R H Dowling^a

^a Gastroenterology Unit, Guy's Hospital Campus, UMDS, London, UK, ^b Microbiology Department, St Thomas' Hospital Campus, UMDS, London, UK, ^c Departments of Microbiology and Medicine, Virginia Commonwealth University, Richmond, Virginia, USA

Correspondence to: Professor R H Dowling, Academic Gastroenterology, 4th Floor N Wing, St Thomas' Hospital, London SE1 7EH, UK. h.dowling{at}umds.ac.uk/ h.dowling{at}talk21.com

Accepted for publication 15 March 2001

BACKGROUND $---$ Deoxycholic acid (DCA), implicated in the pathogenesis of gall stones and colorectal cancer, is mainly formed by bacterialdeconjugation (cholylglycine hydrolase (CGH)) and 7 $alpha$ -dehydroxylation(7 $alpha$ -dehydroxylase (7 $alpha$ -DH)) of conjugated cholic acid (CA) in thecaecum/proximal colon. Despite this, most previous studies ofCGH and 7 $alpha$ -DH have been in faeces rather than in caecal contents.In bacteria, CA increases 7 $alpha$ -DH activity by substrate-enzyme inductionbut little is known about CA concentrations or CA/7 $alpha$ -DH inductionin the humancolon.
AIMS AND METHODS $---$ Therefore, in fresh "faeces", and in caecal aspirates obtained during colonoscopy from 20 patients, we: (i) compared the activitiesof CGH and 7 $alpha$ -DH, (ii) measured 7 $alpha$ -DH in patients with "low" and"high" percentages of DCA in fasting serum (less than and greaterthan the median), (iii) studied CA concentrations in the rightand left halves of the colon, and examined the relationships between(iv) 7 $alpha$ -DH activity and CA concentration in caecal samples (evidenceof substrate-enzyme induction), and (v) 7 $alpha$ -DH and per cent DCAinserum.
RESULTS $---$ Although mean CGH activity in the proximal colon (18.3 (SEM 4.40) ×10² U/mg protein) was comparable with that in "faeces" (16.0 (4.10)×10² U/mg protein) , mean 7 $alpha$ -DH in the caecum (8.54 (1.08) ×10^-4 U/mg protein) was higher (p<0.05) than that in the left colon(5.72 (0.85) ×10^-4 U/mg protein). At both sites, 7 $alpha$ -DH was significantly greaterin the "high" than in the "low" serum DCA subgroups. CA concentrationsin the right colon (0.94 (0.08) µmol/ml) were higher than thosein the left (0.09 (0.03) µmol/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 between 7 $alpha$ -DH and CA concentration.At both sites, 7 $alpha$ -DH was linearly related (p<0.005) to per centDCA inserum.
INTERPRETATION/SUMMARY $---$ These results: (i) confirm that there are marked regional differences in bile acid metabolism between the right and left halvesof the colon, (ii) suggest that caecal and faecal 7 $alpha$ -DH influenceper cent DCA in serum (and, by inference, in bile), and (iii)show that the substrate CA induces the enzyme 7 $alpha$ -DH in thecaecum.

Keywords: deoxycholic acid; 7 $alpha$ -dehydroxylation; gall stones; colorectal cancer

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