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 stones and colorectal cancer, is mainly formed by bacterial deconjugation (cholylglycine hydrolase (CGH)) and 7α-dehydroxylation (7α-dehydroxylase (7α-DH)) of conjugated cholic acid (CA) in the caecum/proximal colon. Despite t...

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Bibliographic Details
Published in:Gut 2001-12, Vol.49 (6), p.835-842
Main Authors: Thomas, L A, Veysey, M J, French, G, Hylemon, P B, Murphy, G M, Dowling, R H
Format: Article
Language:English
Subjects:
7α-dehydroxylation
Acids
Aged
Amidohydrolases - analysis
Amidohydrolases - metabolism
Bile
Biological and medical sciences
Cecum
Cholelithiasis - metabolism
Cholic Acid - analysis
Cholic Acid - metabolism
Colon
colorectal cancer
deoxycholic acid
Deoxycholic Acid - blood
Deoxycholic Acid - metabolism
Feces - enzymology
Female
Fundamental and applied biological sciences. Psychology
gall stones
Gastrointestinal Contents - chemistry
Humans
Hydroxysteroid Dehydrogenases
Intestine. Mesentery
Male
Middle Aged
Oxidoreductases
Rodents
Steroid Hydroxylases - blood
Steroid Hydroxylases - metabolism
Vertebrates: digestive system
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Summary:BACKGROUND Deoxycholic acid (DCA), implicated in the pathogenesis of gall stones and colorectal cancer, is mainly formed by bacterial deconjugation (cholylglycine hydrolase (CGH)) and 7α-dehydroxylation (7α-dehydroxylase (7α-DH)) of conjugated cholic acid (CA) in the caecum/proximal colon. Despite this, most previous studies of CGH and 7α-DH have been in faeces rather than in caecal contents. In bacteria, CA increases 7α-DH activity by substrate-enzyme induction but little is known about CA concentrations or CA/7α-DH induction in the human colon. AIMS AND METHODS Therefore, in fresh “faeces”, and in caecal aspirates obtained during colonoscopy from 20 patients, we: (i) compared the activities of CGH and 7α-DH, (ii) measured 7α-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 the colon, and examined the relationships between (iv) 7α-DH activity and CA concentration in caecal samples (evidence of substrate-enzyme induction), and (v) 7α-DH and per cent DCA in serum. RESULTS Although mean CGH activity in the proximal colon (18.3 (SEM 4.40) ×10−2 U/mg protein) was comparable with that in “faeces” (16.0 (4.10) ×10− 2 U/mg protein) , mean 7α-DH in the caecum (8.54 (1.08) ×10-4 U/mg protein) was higher (p
ISSN:0017-5749
1468-3288
1458-3288
DOI:10.1136/gut.49.6.835