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. 1994 Aug;35(8):1116–1120. doi: 10.1136/gut.35.8.1116

Apparent selective bile acid malabsorption as a consequence of ileal exclusion: effects on bile acid, cholesterol, and lipoprotein metabolism.

J E Akerlund 1, I Björkhem 1, B Angelin 1, L Liljeqvist 1, K Einarsson 1
PMCID: PMC1375066  PMID: 7926917

Abstract

A new model has been developed to characterise the effect of a standardised ileal exclusion on bile acid, cholesterol, and lipoprotein metabolism in humans. Twelve patients treated by colectomy and ileostomy for ulcerative colitis were studied on two occasions: firstly with a conventional ileostomy and then three months afterwards with an ileal pouch operation with an ileoanal anastomosis and a protective loop ileostomy, excluding on average 95 cm of the distal ileum. The ileostomy contents were collected during 96 hours and the excretion of bile acids and cholesterol was determined using gas chromatography-mass spectrometry. Fasting blood and duodenal bile samples were collected on two consecutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased four to five times without any change in cholesterol excretion. Serum concentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycerides were also increased whereas the concentrations of total and LDL cholesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The results show that the exclusion of about 95 cm of distal ileum causes malabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids and cholesterol in the liver. It is suggested that bile acids can regulate cholesterol synthesis by a mechanism independent of the effect of bile acids on cholesterol absorption. The enhanced demand for cholesterol also leads to a decrease in plasma LDL cholesterol and apolipoprotein B concentrations. The malabsorption of bile acids did not affect biliary lipid composition or cholesterol saturations of VLDL triglycerides.

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Selected References

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  1. Akerlund J. E., Björkhem I. Studies on the regulation of cholesterol 7 alpha-hydroxylase and HMG-CoA reductase in rat liver: effects of lymphatic drainage and ligation of the lymph duct. J Lipid Res. 1990 Dec;31(12):2159–2166. [PubMed] [Google Scholar]
  2. Akerlund J. E., Reihnér E., Angelin B., Rudling M., Ewerth S., Björkhem I., Einarsson K. Hepatic metabolism of cholesterol in Crohn's disease. Effect of partial resection of ileum. Gastroenterology. 1991 Apr;100(4):1046–1053. doi: 10.1016/0016-5085(91)90281-o. [DOI] [PubMed] [Google Scholar]
  3. Angelin B., Bjökhem I., Einarsson K. Individual serum bile acid concentrations in normo- and hyperlipoproteinemia as determined by mass fragmentography: relation to bile acid pool size. J Lipid Res. 1978 Jul;19(5):527–537. [PubMed] [Google Scholar]
  4. Angelin B., Björkhem I., Einarsson K., Ewerth S. Hepatic uptake of bile acids in man. Fasting and postprandial concentrations of individual bile acids in portal venous and systemic blood serum. J Clin Invest. 1982 Oct;70(4):724–731. doi: 10.1172/JCI110668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Angelin B., Einarsson K., Hellström K. Evidence for the absorption of bile acids in the proximal small intestine of normo- and hyperlipidaemic subjects. Gut. 1976 Jun;17(6):420–425. doi: 10.1136/gut.17.6.420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Angelin B., Einarsson K., Leijd B. Biliary lipid composition during treatment with different hypolipidaemic drugs. Eur J Clin Invest. 1979 Jun;9(3):185–190. doi: 10.1111/j.1365-2362.1979.tb00921.x. [DOI] [PubMed] [Google Scholar]
  7. Angelin B., Leijd B., Hultcrantz R., Einarsson K. Increased turnover of very low density lipoprotein triglyceride during treatment with cholestyramine in familial hypercholesterolaemia. J Intern Med. 1990 Mar;227(3):201–206. doi: 10.1111/j.1365-2796.1990.tb00143.x. [DOI] [PubMed] [Google Scholar]
  8. Björkhem I., Blomstrand R., Svensson L. Serum cholesterol determination by mass fragmentography. Clin Chim Acta. 1974 Jul 31;54(2):185–193. doi: 10.1016/0009-8981(74)90236-8. [DOI] [PubMed] [Google Scholar]
  9. Björkhem I., Kallner A. Hepatic 7alpha-hydroxylation of cholesterol in ascorbate-deficient and ascorbate-supplemented guinea pigs. J Lipid Res. 1976 Jul;17(4):360–365. [PubMed] [Google Scholar]
  10. Björkhem I., Miettinen T., Reihnér E., Ewerth S., Angelin B., Einarsson K. Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reductase in human liver. J Lipid Res. 1987 Oct;28(10):1137–1143. [PubMed] [Google Scholar]
  11. Björkhem I., Reihnér E., Angelin B., Ewerth S., Akerlund J. E., Einarsson K. On the possible use of the serum level of 7 alpha-hydroxycholesterol as a marker for increased activity of the cholesterol 7 alpha-hydroxylase in humans. J Lipid Res. 1987 Aug;28(8):889–894. [PubMed] [Google Scholar]
  12. Buchwald H., Varco R. L., Matts J. P., Long J. M., Fitch L. L., Campbell G. S., Pearce M. B., Yellin A. E., Edmiston W. A., Smink R. D., Jr Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH) N Engl J Med. 1990 Oct 4;323(14):946–955. doi: 10.1056/NEJM199010043231404. [DOI] [PubMed] [Google Scholar]
  13. Campos C. T., Matts J. P., Fitch L. L., Speech J. C., Long J. M., Buchwald H. Lipid results of partial ileal bypass in patients with heterozygous, type II-A hyperlipoproteinemia. Program on the Surgical Control of the Hyperlipidemias. Surgery. 1990 Oct;108(4):601–611. [PubMed] [Google Scholar]
  14. Carey M. C. Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res. 1978 Nov;19(8):945–955. [PubMed] [Google Scholar]
  15. Carlson K. Lipoprotein fractionation. J Clin Pathol Suppl (Assoc Clin Pathol) 1973;5:32–37. doi: 10.1136/jcp.s1-5.1.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Carrella M., Ericsson S., Del Piano C., Angelin B., Einarsson K. Effect of cholestyramine treatment on biliary lipid secretion rates in normolipidaemic men. J Intern Med. 1991 Mar;229(3):241–246. doi: 10.1111/j.1365-2796.1991.tb00338.x. [DOI] [PubMed] [Google Scholar]
  17. Dowling R. H., Bell G. D., White J. Lithogenic bile in patients with ileal dysfunction. Gut. 1972 Jun;13(6):415–420. doi: 10.1136/gut.13.6.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ewerth S., Angelin B., Einarsson K., Nilsell K., Björkhem I. Serum concentrations of ursodeoxycholic acid in portal venous and systemic venous blood of fasting humans as determined by isotope dilution-mass spectrometry. Gastroenterology. 1985 Jan;88(1 Pt 1):126–133. doi: 10.1016/s0016-5085(85)80144-x. [DOI] [PubMed] [Google Scholar]
  19. Fausa O., Skålhegg B. A. Quantitative determination of bile acids and their conjugates using thin-layer chromatography and a purified 3alpha-hydroxysteroid dehydrogenase. Scand J Gastroenterol. 1974;9(3):249–254. [PubMed] [Google Scholar]
  20. Färkkilä M. A. Biliary cholesterol and lithogeneity of bile in patients after ileal resection. Surgery. 1988 Jul;104(1):18–25. [PubMed] [Google Scholar]
  21. Färkkilä M. A., Tilvis R. S., Miettinen T. A. Cholesterol absorption regulates cholesterol metabolism and plasma lipoprotein levels in patients with gut exclusions. Gastroenterology. 1988 Mar;94(3):582–589. doi: 10.1016/0016-5085(88)90227-2. [DOI] [PubMed] [Google Scholar]
  22. Garbutt J. T., Heaton K. W., Lack L., Tyor M. P. Increased ratio of glycine- to taurine-conjugated bile salts in patients with ileal disorders. Gastroenterology. 1969 Apr;56(4):711–720. [PubMed] [Google Scholar]
  23. Grundy S. M., Ahrens E. H., Jr, Salen G. Interruption of the enterohepatic circulation of bile acids in man: comparative effects of cholestyramine and ileal exclusion on cholesterol metabolism. J Lab Clin Med. 1971 Jul;78(1):94–121. [PubMed] [Google Scholar]
  24. Heaton K. W. Disturbances of bile acid metabolism in intestinal disease. Clin Gastroenterol. 1977 Jan;6(1):69–89. [PubMed] [Google Scholar]
  25. Heaton K. W., Read A. E. Gall stones in patients with disorders of the terminal ileum and disturbed bile salt metabolism. Br Med J. 1969 Aug 30;3(5669):494–496. doi: 10.1136/bmj.3.5669.494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Koivisto P. V., Miettinen T. A. Effect of ileal exclusion on kinetics of very low density lipoprotein triglycerides in familial hypercholesterolemia. Clin Chim Acta. 1986 Nov 30;161(1):91–101. doi: 10.1016/0009-8981(86)90266-4. [DOI] [PubMed] [Google Scholar]
  27. Krag E., Phillips S. F. Active and passive bile acid absorption in man. Perfusion studies of the ileum and jejunum. J Clin Invest. 1974 Jun;53(6):1686–1694. doi: 10.1172/JCI107720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Little J. M., Avramovic J. Gallstone formation after major abdominal surgery. Lancet. 1991 May 11;337(8750):1135–1137. doi: 10.1016/0140-6736(91)92796-5. [DOI] [PubMed] [Google Scholar]
  29. Lopes-Virella M. F., Stone P., Ellis S., Colwell J. A. Cholesterol determination in high-density lipoproteins separated by three different methods. Clin Chem. 1977 May;23(5):882–884. [PubMed] [Google Scholar]
  30. Lund E., Sisfontes L., Reihner E., Bjorkhem I. Determination of serum levels of unesterified lathosterol by isotope dilution-mass spectrometry. Scand J Clin Lab Invest. 1989 Apr;49(2):165–171. doi: 10.3109/00365518909105417. [DOI] [PubMed] [Google Scholar]
  31. Roda A., Festi D., Sama C., Mazzella G., Alini R., Roda E., Barbara L. Enzymatic determination of cholesterol in bile. Clin Chim Acta. 1975 Nov 3;64(3):337–341. doi: 10.1016/0009-8981(75)90364-2. [DOI] [PubMed] [Google Scholar]
  32. Rouser G., Fkeischer S., Yamamoto A. Two dimensional then layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids. 1970 May;5(5):494–496. doi: 10.1007/BF02531316. [DOI] [PubMed] [Google Scholar]
  33. Rutgeerts P., Ghoos Y., Vantrappen G. Effects of partial ileocolectomy and Crohn's disease on biliary lipid secretion. Dig Dis Sci. 1987 Nov;32(11):1231–1238. doi: 10.1007/BF01296371. [DOI] [PubMed] [Google Scholar]
  34. Schaffer R., Sniegoski L. T., Welch M. J., White V. E., Cohen A., Hertz H. S., Mandel J., Paule R. C., Svensson L., Björkhem I. Comparison of two isotope dilution/mass spectrometric methods for determination of total serum cholesterol. Clin Chem. 1982 Jan;28(1):5–8. [PubMed] [Google Scholar]
  35. Wise L., Stein T. The effect of jejunoileal bypass on bile composition and the formation of billiary calculi. Ann Surg. 1978 Jan;187(1):57–62. doi: 10.1097/00000658-197801000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]

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