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 7 alpha-dehydroxylation (7 alpha-dehydroxylase (7 alpha-DH)) of conjugated cholic acid (CA) in the caecum/proximal colon. Despite this, most previous studies of CGH and 7 alpha-DH have been in faeces rather than in caecal contents. In bacteria, CA increases 7 alpha-DH activity by substrate-enzyme induction but little is known about CA concentrations or CA/7 alpha-DH induction in the human colon.


OBJECTIVE
Therefore, in fresh "faeces", and in caecal aspirates obtained during colonoscopy from 20 patients, we: (i) compared the activities of 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 greater than the median), (iii) studied CA concentrations in the right and left halves of the colon, and examined the relationships between (iv) 7 alpha-DH activity and CA concentration in caecal samples (evidence of substrate-enzyme induction), 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) x10(-2) U/mg protein) was comparable with that in "faeces" (16.0 (4.10) x10(- 2) U/mg protein), mean 7 alpha-DH in the caecum (8.54 (1.08) x10(-4) U/mg protein) was higher (p<0.05) than that in the left colon (5.72 (0.85) x10(-4) U/mg protein). At both sites, 7 alpha-DH was significantly greater in the "high" than in the "low" serum DCA subgroups. CA concentrations in the right colon (0.94 (0.08) micromol/ml) were higher than those in the left (0.09 (0.03) micromol/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 cent DCA in serum. INTERPRETATION/SUMMARY: These results: (i) confirm that there are marked regional differences in bile acid metabolism between the right and left halves of the colon, (ii) suggest that caecal and faecal 7 alpha-DH influence per cent DCA in serum (and, by inference, in bile), and (iii) show that the substrate CA induces the enzyme 7 alpha-DH in the caecum.
Thomas
L A
LA
Gastroenterology Unit, Guy's Hospital Campus, UMDS, London, UK.
Veysey
M J
MJ
French
G
G
Hylemon
P B
PB
Murphy
G M
GM
Dowling
R H
RH
D000368:Aged; D000581:Amidohydrolases / Q000032:analysis / Q000378:metabolism*; D002432:Cecum; D002769:Cholelithiasis / Q000378:metabolism*; D019826:Cholic Acid / Q000032:analysis / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000097:blood / Q000378:metabolism*; D005243:Feces / Q000201:enzymology; D005260:Female; D005766:Gastrointestinal Contents / Q000737:chemistry*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases; D013250:Steroid Hydroxylases / Q000097:blood / Q000378:metabolism*
D003840:Deoxycholic Acid; D010088:Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases; C025376:7 alpha-hydroxysteroid dehydrogenase; D013250:Steroid Hydroxylases; D000581:Amidohydrolases; C023154:choloylglycine hydrolase; D019826:Cholic Acid