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. 2001 Dec;49(6):835–842. doi: 10.1136/gut.49.6.835

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

L Thomas 1, M Veysey 1, G French 1, P Hylemon 1, G Murphy 1, R Dowling 1
PMCID: PMC1728526  PMID: 11709519

Abstract

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.


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

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Figure 1  .

Figure 1  

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Paired results for cholylglycine hydrolase activity in "caecal" and faecal samples: individual data points with means (SEM).

Figure 2  .

Figure 2  

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Paired results for 7α-dehydroxylase activity in the "caecal" and faecal samples: individual data points with means (SEM).

Figure 3  .

Figure 3  

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Paired results linking "caecal" and faecal 7α-dehydroxylase activities in the low (A) versus high (B) serum deoxycholic acid (DCA) subgroups: individual data points with means (SEM).

Figure 4  .

Figure 4  

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Non-paired results comparing "caecal" (A) and faecal (B) 7α-dehydroxylase activities in the low versus high serum deoxycholic acid (DCA) subgroups: individual data points with means (SEM).

Figure 5  .

Figure 5  

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Endogenous cholic acid concentrations in paired "caecal" and faecal samples: individual data points with means (SEM).

Figure 6  .

Figure 6  

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Relationship between 7α-dehydroxylase activity and cholic acid concentration in the "caecal" samples.

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