Home LiteratureArticle Details
PMID: 11709519 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

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

Gut ·Vol. 49 ·No. 6 ·2001-12-00 ·Pages 835-42

Thomas LA, Veysey MJ, French G, Hylemon PB, Murphy GM, Dowling RH

Abstract

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. 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. 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.

MeSH Terms
Aged Amidohydrolases/analysis,metabolism Cecum Cholelithiasis/metabolism Cholic Acid/analysis,metabolism Deoxycholic Acid/blood,metabolism Feces/enzymology Female Gastrointestinal Contents/chemistry Humans Hydroxysteroid Dehydrogenases Male Middle Aged Oxidoreductases Steroid Hydroxylases/blood,metabolism
Chemicals
Deoxycholic Acid Oxidoreductases Hydroxysteroid Dehydrogenases 7 alpha-hydroxysteroid dehydrogenase Steroid Hydroxylases Amidohydrolases choloylglycine hydrolase Cholic Acid
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Thomas L A
Gastroenterology Unit, Guy's Hospital Campus, UMDS, London, UK.
Veysey M J
French G
Hylemon P B
Murphy G M
Dowling R H
References (35)
35 references, click to expand
  1. Bile acid induction specificity of 7 alpha-dehydroxylase activity in an intestinal Eubacterium species.
    Steroids. 1980 Jan;35(1):103-9 PMID: 7376208
  2. Do colonic bacteria contribute to cholesterol gall-stone formation? Effects of lactulose on bile.
    Br Med J (Clin Res Ed). 1981 Mar 28;282(6269):1018-20 PMID: 6783227
  3. Factors in the mechanism of diarrhea in bile acid malabsorption: fecal pH--a key determinant.
    Gastroenterology. 1981 Jun;80(6):1454-64 PMID: 7227771
  4. Serum bile acid analysis.
    Clin Chim Acta. 1983 Jan 7;127(1):1-17 PMID: 6337748
  5. Intestinal transit, deoxycholic acid and the cholesterol saturation of bile--three inter-related factors.
    Gut. 1986 May;27(5):550-8 PMID: 3699564
  6. Studies on steroids. CCXXVIII Trace analysis of bile acids by gas chromatography-mass spectrometry with negative ion chemical ionization detection.
    J Chromatogr. 1987 Feb 13;388(2):379-87 PMID: 3558654
  7. Inhibition of secondary bile acid formation in the large intestine by lactulose in healthy subjects of two different age groups.
    Eur J Clin Invest. 1988 Feb;18(1):56-61 PMID: 3130260
  8. Measurement of gastrointestinal pH profiles in normal ambulant human subjects.
    Gut. 1988 Aug;29(8):1035-41 PMID: 3410329
  9. Determination of plasma bile acids by capillary gas-liquid chromatography-electron capture negative chemical ionization mass fragmentography.
    J Lipid Res. 1989 Oct;30(10):1647-52 PMID: 2614267
  10. pH-profile and regional transit times of the normal gut measured by a radiotelemetry device.
    Aliment Pharmacol Ther. 1989 Dec;3(6):605-13 PMID: 2518873
  11. The bile acid-inducible baiB gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A ligase.
    J Bacteriol. 1992 Apr;174(7):2065-71 PMID: 1551828
  12. Deoxycholic acid metabolism in patients with adenomas.
    Gastroenterology. 1993 Sep;105(3):955-6 PMID: 8359667
  13. Performance characteristics of reversed-phase bonded silica cartridges for serum bile acid extraction.
    Biomed Chromatogr. 1996 Jan-Feb;10(1):1-5 PMID: 8821862
  14. 7 alpha-dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones.
    Gastroenterology. 1996 Dec;111(6):1611-20 PMID: 8942741
  15. Assessment of fecal bacteria with bile acid 7 alpha-dehydroxylating activity for the presence of bai-like genes.
    Appl Environ Microbiol. 1997 Mar;63(3):1185-8 PMID: 9055436
  16. Cholylglycine hydrolase and 7alpha-dehydroxylase optimum assay conditions in vitro and caecal enzyme activities ex vivo.
    Clin Chim Acta. 1997 Dec 10;268(1-2):61-72 PMID: 9495571
  17. Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis.
    Am J Gastroenterol. 1998 Sep;93(9):1498-504 PMID: 9732932
  18. Turnover and nature of fecal bile acids in germfree and infected rats fed cholic acid-24-14C; bile acids and steroids 41.
    Proc Soc Exp Biol Med. 1957 Mar;94(3):467-71 PMID: 13408295
  19. THIN-LAYER CHROMATOGRAPHY OF BILE ACIDS.
    J Lipid Res. 1963 Jan;4:11-6 PMID: 14167657
  20. Mechanism for the transit-induced increase in colonic deoxycholic acid formation in cholesterol cholelithiasis.
    Gastroenterology. 2000 Sep;119(3):806-15 PMID: 10982775
  21. Colonic transit influences deoxycholic acid kinetics.
    Gastroenterology. 2001 Oct;121(4):812-22 PMID: 11606495
  22. Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial.
    Gut. 2001 Dec;49(6):828-34 PMID: 11709518
  23. Isolated fecal microorganisms capable of 7-alpha-dehydroxylating bile acids.
    J Exp Med. 1966 Feb 1;123(2):413-32 PMID: 5325994
  24. Distribution of disaccharidase activity in the small bowel of normal and lactase-deficient subjects.
    Gastroenterology. 1966 Oct;51(4):481-8 PMID: 5922947
  25. The enzymatic cleavage of the carbon-nitrogen bond in 3-alpha, 7-alpha, 12-alpha-trihydroxy-5-beta-cholan-24-oylglycine.
    J Biol Chem. 1967 Jan 10;242(1):7-11 PMID: 6016335
  26. Degradation of bile salts by human intestinal bacteria.
    Gut. 1968 Feb;9(1):22-7 PMID: 5640921
  27. Absorption of bile acids from the large bowel in man.
    J Clin Invest. 1968 Sep;47(9):2070-8 PMID: 5675427
  28. Degradation of bile salts by human intestinal bacteria.
    Gut. 1969 Jul;10(7):575-6 PMID: 5806939
  29. Quantitative determination of the major 3-hydroxy bile acids in biological material after thin-layer chromatographic separation.
    Clin Chim Acta. 1970 Jun;28(3):495-504 PMID: 5450173
  30. Mass movements and intracolonic pressures.
    Am J Dig Dis. 1971 Aug;16(8):693-6 PMID: 5096782
  31. The microflora of the human ileum and intrabdominal colon: results of direct needle aspiration at surgery and evaluation of the technique.
    J Lab Clin Med. 1972 Mar;79(3):421-9 PMID: 4551448
  32. Postprandial concentrations of free and conjugated bile acids down the length of the normal human small intestine.
    Gut. 1973 Jul;14(7):513-8 PMID: 4729918
  33. Individual bile acids in portal venous and systemic blood serum of fasting man.
    Gastroenterology. 1977 Dec;73(6):1377-82 PMID: 913977
  34. Colonic bacterial activity, biliary cholesterol saturation, and pathogenesis of gallstones.
    Lancet. 1978 Nov 18;2(8099):1063-5 PMID: 82084
  35. 7alpha-Dehydroxylation of cholic acid and chenodeoxycholic acid by Clostridium leptum.
    J Lipid Res. 1979 Mar;20(3):325-33 PMID: 36438
Article Info
Journal
Gut
Abbr.
Gut
ISSN
0017-5749
DOI
10.1136/gut.49.6.835
Published
2001-12-00
Pages
835-42
Language
English
Region
England
NLM ID
2985108R
PMCID
PMC1728526
Subset
IM
External Links
PubMed source DOI: 10.1136/gut.49.6.835 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2