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British Medical Journal (Clinical Research Ed.) logoLink to British Medical Journal (Clinical Research Ed.)
. 1981 Mar 28;282(6269):1018–1020. doi: 10.1136/bmj.282.6269.1018

Do colonic bacteria contribute to cholesterol gall-stone formation? Effects of lactulose on bile.

J R Thornton, K W Heaton
PMCID: PMC1504907  PMID: 6783227

Abstract

Ten healthy middle-aged women volunteered for a study to test the effect of lactulose--a synthetic, non-absorbable disaccharide--on the colonic metabolism of bile acids and on bile lipid composition. Lactulose (60 g daily in eight cases, 39 g daily in two) was taken as a proprietary syrup for six weeks, and bile was collected by duodenal intubation before and immediately after six weeks. All subjects showed a fall in the percentage of the 7-alpha-dehydroxylated bile acid deoxycholic acid (mean 28.4 +/- SEM 3.7 to 15.6 +/- 2.4; p less than 0.002) and a rise in the percentage of the primary bile acid chenodeoxycholic acid (mean 33.2 +/- 42.9 +/- 2.9; p less than 0.001). The percentage of cholic acid rose in eight subjects but mean values did not differ significantly. Bile was initially super-saturated with cholesterol in most subjects and became less saturated with cholesterol in all but one (mean saturation index 1.40 +/- 0.11 to 1.19 +/- 0.07; p less these 0.005). These data support the theory colonic bacteria contribute to cholesterol gall-stone formation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahlberg J., Angelin B., Einarsson K., Hellstrom K., Leijd B. Influence of deoxycholic acid on biliary lipids in man. Clin Sci Mol Med. 1977 Sep;53(3):249–256. doi: 10.1042/cs0530249. [DOI] [PubMed] [Google Scholar]
  2. Andersen J. M. Chenodeoxycholic acid desaturates bile--but how? Gastroenterology. 1979 Nov;77(5):1146–1151. [PubMed] [Google Scholar]
  3. Aries V., Hill M. J. Degradation of steroids by intestinal bacteria. II. Enzymes catalysing the oxidoreduction of the 3 alpha-, 7 alpha- and 12 alpha-hydroxyl groups in cholic acid, and the dehydroxylation of the 7-hydroxyl group. Biochim Biophys Acta. 1970 May 5;202(3):535–543. doi: 10.1016/0005-2760(70)90124-4. [DOI] [PubMed] [Google Scholar]
  4. Bolton C. H., Low-Beer T. S., Pomare E. W., Wicks A. C., Yeates J., Heaton K. W. A simplified procedure for the analysis of cholesterol, phospholipids and bile salts in human bile. Clin Chim Acta. 1978 Feb 1;83(1-2):177–181. doi: 10.1016/0009-8981(78)90222-x. [DOI] [PubMed] [Google Scholar]
  5. Bown R. L., Gibson J. A., Sladen G. E., Hicks B., Dawson A. M. Effects of lactulose and other laxatives on ileal and colonic pH as measured by a radiotelemetry device. Gut. 1974 Dec;15(12):999–1004. doi: 10.1136/gut.15.12.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carulli N., Ponz de Leon M., Zironi F., Iori R., Loria P. Bile acid feeding and hepatic sterol metabolism: effect of deoxycholic acid. Gastroenterology. 1980 Oct;79(4):637–641. [PubMed] [Google Scholar]
  7. Cummings J. H., Hill M. J., Jenkins D. J., Pearson J. R., Wiggins H. S. Changes in fecal composition and colonic function due to cereal fiber. Am J Clin Nutr. 1976 Dec;29(12):1468–1473. doi: 10.1093/ajcn/29.12.1468. [DOI] [PubMed] [Google Scholar]
  8. Eastwood M. A., Hamilton D. Studies on the adsorption of bile salts to non-absorbed components of diet. Biochim Biophys Acta. 1968 Jan 10;152(1):165–173. doi: 10.1016/0005-2760(68)90018-0. [DOI] [PubMed] [Google Scholar]
  9. Hegardt F. G., Dam H. The solubility of cholesterol in aqueous solutions of bile salts and lecithin. Z Ernahrungswiss. 1971 Apr;10(3):223–233. doi: 10.1007/BF02020933. [DOI] [PubMed] [Google Scholar]
  10. Igimi H., Carey M. C. pH-Solubility relations of chenodeoxycholic and ursodeoxycholic acids: physical-chemical basis for dissimilar solution and membrane phenomena. J Lipid Res. 1980 Jan;21(1):72–90. [PubMed] [Google Scholar]
  11. LaRusso N. F., Szczepanik P. A., Hofmann A. F. Effect of deoxycholic acid ingestion on bile acid metabolism and biliary lipid secretion in normal subjects. Gastroenterology. 1977 Jan;72(1):132–140. [PubMed] [Google Scholar]
  12. Low-Beer T. S., Nutter S. Colonic bacterial activity, biliary cholesterol saturation, and pathogenesis of gallstones. Lancet. 1978 Nov 18;2(8099):1063–1065. doi: 10.1016/s0140-6736(78)91800-7. [DOI] [PubMed] [Google Scholar]
  13. Low-Beer T. S., Pomare E. W. Can colonic bacterial metabolites predispose to cholesterol gall stones? Br Med J. 1975 Feb 22;1(5955):438–440. doi: 10.1136/bmj.1.5955.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Macdonald I. A., Singh G., Mahony D. E., Meier C. E. Effect of pH on bile salt degradation by mixed fecal cultures. Steroids. 1978 Sep;32(2):245–256. doi: 10.1016/0039-128x(78)90009-0. [DOI] [PubMed] [Google Scholar]
  15. Midtvedt T., Norman A. Parameters in 7-alpha-dehydroxylation of bile acids by anaerobic lactobacilli. Acta Pathol Microbiol Scand. 1968;72(2):313–329. doi: 10.1111/j.1699-0463.1968.tb01345.x. [DOI] [PubMed] [Google Scholar]
  16. Pomare E. W., Heaton K. W., Low-Beer T. S., Espiner H. J. The effect of wheat bran upon bile salt metabolism and upon the lipid composition of bile in gallstone patients. Am J Dig Dis. 1976 Jul;21(7):521–526. doi: 10.1007/BF01464757. [DOI] [PubMed] [Google Scholar]
  17. Pomare E. W., Low-Beer T. S. The selective inhibition of chenodeoxycholate synthesis by cholate metabolites in man. Clin Sci Mol Med. 1975 Apr;48(4):315–321. doi: 10.1042/cs0480315. [DOI] [PubMed] [Google Scholar]
  18. Vlahcevic Z. R., Bell C. C., Jr, Juttijudata P., Swell L. Bile-rich duodenal fluid as an indicator of biliary lipid composition and its applicability to detection of lithogenic bile. Am J Dig Dis. 1971 Sep;16(9):797–802. doi: 10.1007/BF02239307. [DOI] [PubMed] [Google Scholar]

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