TY - JOUR
T1 - Bile acid metabolism by fresh human colonic contents
T2 - A comparison of caecal versus faecal samples
AU - Thomas, L. A.
AU - Veysey, M. J.
AU - French, G.
AU - Hylemon, P. B.
AU - Murphy, G. M.
AU - Dowling, R. H.
PY - 2001
Y1 - 2001
N2 - 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<0.05) than that in the left colon (5.72 (0.85) ×10-4 U/mg protein). At both sites, 7α-DH was significantly greater in the "high" than in the "low" serum DCA subgroups. CA concentrations in the right colon (0.94 (0.08) μmol/ml) were higher than those in 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 7α-DH and CA concentration. At both sites, 7α-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 7α-DH influence per cent DCA in serum (and, by inference, in bile), and (iii) show that the substrate CA induces the enzyme 7α-DH in the caecum.
AB - 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<0.05) than that in the left colon (5.72 (0.85) ×10-4 U/mg protein). At both sites, 7α-DH was significantly greater in the "high" than in the "low" serum DCA subgroups. CA concentrations in the right colon (0.94 (0.08) μmol/ml) were higher than those in 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 7α-DH and CA concentration. At both sites, 7α-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 7α-DH influence per cent DCA in serum (and, by inference, in bile), and (iii) show that the substrate CA induces the enzyme 7α-DH in the caecum.
KW - 7α-dehydroxylation
KW - Colorectal cancer
KW - Deoxycholic acid
KW - Gall stones
UR - http://www.scopus.com/inward/record.url?scp=0035181786&partnerID=8YFLogxK
U2 - 10.1136/gut.49.6.835
DO - 10.1136/gut.49.6.835
M3 - Article
C2 - 11709519
AN - SCOPUS:0035181786
SN - 0017-5749
VL - 49
SP - 835
EP - 842
JO - Gut
JF - Gut
IS - 6
ER -