Abstract
Unexplained bile acid malabsorption associated with diarrhoea that responds to cholestyramine was first described in 1973 but convincing evidence of the proposed mechanism--a defective active ileal bile acid transport--has never been substantiated. Active bile acid transport was quantified in vitro using brush border membrane vesicles prepared from terminal ileal biopsy specimens from 10 patients who fulfilled the criteria of idiopathic bile acid diarrhoea. They were recruited from 181 patients with bile acid malabsorption of various causes. Transport was quantified as in vitro Na+ dependent bile acid transport (INBAT), expressed as pmol taurocholate/mg brush border membrane protein/15 seconds, and in vitro Na+ dependent bile acid local transport capacity (INBALTC), expressed as pmol taurocholate/g ileal biopsy tissue/15 seconds. The lowest INBAT and INBALTC values in the 10 patients with idiopathic bile acid diarrhoea were well above the 10th centile values of a control group of 132 patients. Both INBAT (mean (range) 88 (30-136)) and INBALTC (158 (85-268)) values were significantly higher in the 10 patients than in the control group (INBAT: mean (range) 63 (1-244), INBALTC: mean (range) 98 (1-408)). Quantification of active ileal bile acid transport in these 10 patients with idiopathic bile acid malabsorption suggests that a genetic (carrier) defect is rare in adults.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aldini R., Roda A., Festi D., Sama C., Mazzella G., Bazzoli F., Morselli A. M., Roda E., Barbara L. Bile acid malabsorption and bile acid diarrhea in intestinal resection. Dig Dis Sci. 1982 Jun;27(6):495–502. doi: 10.1007/BF01296727. [DOI] [PubMed] [Google Scholar]
- Binder H. J., Filburn C., Volpe B. T. Bile salt alteration of colonic electrolyte transport: role of cyclic adenosine monophosphate. Gastroenterology. 1975 Mar;68(3):503–508. [PubMed] [Google Scholar]
- Blake G., Kennedy T. L., McKelvey S. T. Bile acids and post-vagotomy diarrhoea. Br J Surg. 1983 Mar;70(3):177–179. doi: 10.1002/bjs.1800700313. [DOI] [PubMed] [Google Scholar]
- Conley D. R., Coyne M. J., Bonorris G. G., Chung A., Schoenfield L. J. Bile acid stimulation of colonic adenylate cyclase and secretion in the rabbit. Am J Dig Dis. 1976 Jun;21(6):453–458. doi: 10.1007/BF01072128. [DOI] [PubMed] [Google Scholar]
- Cummings J. H., Wiggins H. S., Jenkins D. J., Houston H., Jivraj T., Drasar B. S., Hill M. J. Influence of diets high and low in animal fat on bowel habit, gastrointestinal transit time, fecal microflora, bile acid, and fat excretion. J Clin Invest. 1978 Apr;61(4):953–963. doi: 10.1172/JCI109020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fondacaro J. D., Heubi J. E., Kellogg F. W. Intestinal bile acid malabsorption in cystic fibrosis: a primary mucosal cell defect. Pediatr Res. 1982 Jun;16(6):494–498. doi: 10.1203/00006450-198206000-00019. [DOI] [PubMed] [Google Scholar]
- Fromm H., Malavolti M. Bile acid-induced diarrhoea. Clin Gastroenterol. 1986 Jul;15(3):567–582. [PubMed] [Google Scholar]
- Fromm H., Thomas P. J., Hofmann A. F. Sensitivity and specificity in tests of distal ileal function: prospective comparison of bile acid and vitamin B 12 absorption in ileal resection patients. Gastroenterology. 1973 Jun;64(6):1077–1090. [PubMed] [Google Scholar]
- Fromm H., Tunuguntla A. K., Malavolti M., Sherman C., Ceryak S. Absence of significant role of bile acids in diarrhea of a heterogeneous group of postcholecystectomy patients. Dig Dis Sci. 1987 Jan;32(1):33–44. doi: 10.1007/BF01296685. [DOI] [PubMed] [Google Scholar]
- GRUNDY S. M., AHRENS E. H., Jr, MIETTINEN T. A. QUANTITATIVE ISOLATION AND GAS--LIQUID CHROMATOGRAPHIC ANALYSIS OF TOTAL FECAL BILE ACIDS. J Lipid Res. 1965 Jul;6:397–410. [PubMed] [Google Scholar]
- Heaton K. W. Functional diarrhoea: the acid test. Br Med J (Clin Res Ed) 1985 May 4;290(6478):1298–1299. doi: 10.1136/bmj.290.6478.1298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heubi J. E., Balistreri W. F., Fondacaro J. D., Partin J. C., Schubert W. K. Primary bile acid malabsorption: defective in vitro ileal active bile acid transport. Gastroenterology. 1982 Oct;83(4):804–811. [PubMed] [Google Scholar]
- Hutcheon D. F., Bayless T. M., Gadacz T. R. Postcholecystectomy diarrhea. JAMA. 1979 Feb 23;241(8):823–824. [PubMed] [Google Scholar]
- Malchow-Møller A., Arffmann S., Larusso N. F., Krag E. Enzymatic determination of total 3 alpha-hydroxy bile acids in faeces. Validation in healthy subjects of a rapid method suitable for clinical routine purpose. Scand J Gastroenterol. 1982 Apr;17(3):331–333. doi: 10.3109/00365528209182063. [DOI] [PubMed] [Google Scholar]
- McJunkin B., Fromm H., Sarva R. P., Amin P. Factors in the mechanism of diarrhea in bile acid malabsorption: fecal pH--a key determinant. Gastroenterology. 1981 Jun;80(6):1454–1464. [PubMed] [Google Scholar]
- Meihoff W. E., Kern F., Jr Bile salt malabsorption in regional ileitis, ileal resection and mannitol-induced diarrhea. J Clin Invest. 1968 Feb;47(2):261–267. doi: 10.1172/JCI105722. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Merrick M. V. Bile acid malabsorption. Clinical presentations and diagnosis. Dig Dis. 1988;6(3):159–169. doi: 10.1159/000171192. [DOI] [PubMed] [Google Scholar]
- Merrick M. V., Eastwood M. A., Ford M. J. Is bile acid malabsorption underdiagnosed? An evaluation of accuracy of diagnosis by measurement of SeHCAT retention. Br Med J (Clin Res Ed) 1985 Mar 2;290(6469):665–668. doi: 10.1136/bmj.290.6469.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Molloy A. M., Tomkin G. H. Altered bile in diabetic diarrhoea. Br Med J. 1978 Nov 25;2(6150):1462–1463. doi: 10.1136/bmj.2.6150.1462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orholm M., Pedersen J. O., Arnfred T., Rødbro P., Thaysen E. H. Evaluation of the applicability of the SeHCAT test in the investigation of patients with diarrhoea. Scand J Gastroenterol. 1988 Jan;23(1):113–117. doi: 10.3109/00365528809093859. [DOI] [PubMed] [Google Scholar]
- Popović O. S., Kostić K. M., Milović V. B., Milutinović-Djurić S., Miletić V. D., Sesić L., Djordjević M., Bulajić M., Bojić P., Rubinić M. Primary bile acid malabsorption. Histologic and immunologic study in three patients. Gastroenterology. 1987 Jun;92(6):1851–1858. [PubMed] [Google Scholar]
- Race T. F., Paes I. C., Faloon W. W. Intestinal malabsorption induced by oral colchicine. Comparison with neomycin and cathartic agents. Am J Med Sci. 1970 Jan;259(1):32–41. doi: 10.1097/00000441-197001000-00005. [DOI] [PubMed] [Google Scholar]
- Rubulis A., Rubert M., Faloon W. W. Cholesterol lowering, fecal bile acid, and sterol changes during neomycin and colchicine. Am J Clin Nutr. 1970 Sep;23(9):1251–1259. doi: 10.1093/ajcn/23.9.1251. [DOI] [PubMed] [Google Scholar]
- Scarpello J. H., Hague R. V., Cullen D. R., Sladen G. E. The 14C-glycocholate test in diabetic diarrhoea. Br Med J. 1976 Sep 18;2(6037):673–675. doi: 10.1136/bmj.2.6037.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schiller L. R., Hogan R. B., Morawski S. G., Santa Ana C. A., Bern M. J., Norgaard R. P., Bo-Linn G. W., Fordtran J. S. Studies of the prevalence and significance of radiolabeled bile acid malabsorption in a group of patients with idiopathic chronic diarrhea. Gastroenterology. 1987 Jan;92(1):151–160. doi: 10.1016/0016-5085(87)90852-3. [DOI] [PubMed] [Google Scholar]
- Stanley M. M., Paul D., Gacke D., Murphy J. Effects of cholestyramine, metamucil, and cellulose on fecal bile salt excretion in man. Gastroenterology. 1973 Dec;65(6):889–894. [PubMed] [Google Scholar]
- Thaysen E. H. Idiopathic bile acid diarrhoea reconsidered. Scand J Gastroenterol. 1985 May;20(4):452–456. doi: 10.3109/00365528509089679. [DOI] [PubMed] [Google Scholar]
- Thaysen E. H., Pedersen L. Diarrhoea associated with idiopathic bile acid malabsorption. Fact or fantasy? Dan Med Bull. 1973 Dec;20(6):174–177. [PubMed] [Google Scholar]
- Thaysen E. H., Pedersen L. Idiopathic bile acid catharsis. Gut. 1976 Dec;17(12):965–970. doi: 10.1136/gut.17.12.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tougaard L., Giese B., Pedersen B. H., Binder V. Bile acid metabolism in patients with Crohn's disease in terminal ileum. Scand J Gastroenterol. 1986 Jun;21(5):627–633. doi: 10.3109/00365528609003110. [DOI] [PubMed] [Google Scholar]
- Weber A. M., Roy C. C., Chartrand L., Lepage G., Dufour O. L., Morin C. L., Lasalle R. Relationship between bile acid malabsorption and pancreatic insufficiency in cystic fibrosis. Gut. 1976 Apr;17(4):295–299. doi: 10.1136/gut.17.4.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Rooij F. W., van den Berg J. W., Sinaasappel M., Bosman-Jacobs E. P., Touw-Blommesteijn A. C. Bile acid malabsorption in cystic fibrosis; membrane vesicles, a tool for revealing the role of the ileal brush border membrane. Acta Paediatr Scand Suppl. 1985;317:28–30. doi: 10.1111/j.1651-2227.1985.tb14931.x. [DOI] [PubMed] [Google Scholar]
- de Wael J., Raaymakers C. E., Endeman H. J. Simplified quantitative determination of total fecal bile acids. Clin Chim Acta. 1977 Sep 1;79(2):465–470. doi: 10.1016/0009-8981(77)90443-0. [DOI] [PubMed] [Google Scholar]
- van Blankenstein M., Hoyset T., Hörchner P., Frenkel M., Wilson J. H. Faecal bile acid radioactivity, a sensitive and relatively simple test for ileal dysfunction. Neth J Med. 1977;20(6):248–252. [PubMed] [Google Scholar]
- van Tilburg A. J., de Rooij F. W., van Blankenstein M., van den Berg J. W., Bosman-Jacobs E. P. Na+-dependent bile acid transport in the ileum: the balance between diarrhea and constipation. Gastroenterology. 1990 Jan;98(1):25–32. doi: 10.1016/0016-5085(90)91286-f. [DOI] [PubMed] [Google Scholar]