New Insights into Bile Acid Malabsorption

详细信息    查看全文

• 作者：Ian Johnston (1) (2)
  Jonathan Nolan (1) (2)
  Sanjeev S. Pattni (1) (2)
  Julian R. F. Walters (1) (2)
  
• 关键词：Chronic diarrhea ; Bile acid malabsorption ; Irritable bowel syndrome ; CYP7A1 ; Bile acid synthesis ; SeHCAT ; 7α ; hydroxy ; 4 ; cholesten ; 3 ; one ; Fibroblast growth factor 19 ; Negative feedback ; Liver ; Ileum ; Enterohepatic circulation ; Bile acid sequestrants
• 刊名：Current Gastroenterology Reports
• 出版年：2011
• 出版时间：October 2011
• 年：2011
• 卷：13
• 期：5
• 页码：418-425
• 全文大小：349KB
• 参考文献：1. Hofmann AF. The syndrome of ileal disease and the broken enterohepatic circulation: cholerheic enteropathy. Gastroenterology. 1967;52:752-.
  2. -Hofmann AF: Bile acids: trying to understand their chemistry and biology with the hope of helping patients. / Hepatology 2009;49:1403-8. / A personal review of the development of the understanding of bile acids and their roles in disease.
  3. Pattni SS, Walters JRF. Recent advances in the understanding of bile acid malabsorption. Brit Med Bull. 2009;92:79-3. CrossRef
  4. ?-Walters JRF, Tasleem AM, Omer OS, et al.: A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. / Clin Gastro Hepatol 2009;7:1189-4. / Description of reduced FGF19 levels in patients with chronic diarrhea.
  5. Hofmann AF, Mangelsdorf DJ, Kliewer SA. Chronic diarrhea due to excessive bile acid synthesis and not defective ileal transport: a new syndrome of defective fibroblast growth factor 19 release. Clin Gastroenterol Hepatol. 2009;7:1151-. CrossRef
  6. Khalid U, Lalji A, Stafferton R, Andreyev J. Bile acid malabsorption: a forgotten diagnosis? Clin Medicine. 2010;10:124-.
  7. Walters JR. Defining primary bile acid diarrhea: making the diagnosis and recognizing the disorder. Expert Rev Gastroenterol Hepatol. 2010;4:561-. CrossRef
  8. Fromm H, Malavolti M. Bile acid-induced diarrhoea. Clin Gastroenterol. 1986;15:567-2.
  9. Thaysen EH, Pedersen L. Idiopathic bile acid catharsis. Gut. 1976;17:965-0. CrossRef
  10. Williams AJK, Merrick MV, Eastwood MA. Idiopathic bile acid malabsorption—a review of clinical presentation, diagnosis, and response to treatment. Gut. 1991;32:1004-. CrossRef
  11. Russell DW. Fifty years of advances in bile acid synthesis and metabolism. J Lipid Res. 2009;50(Suppl):S120-. CrossRef
  12. Low-Beer TS, Pomare EW. Regulation of bile salt pool size in man. Br Med J. 1973;2:338-0. CrossRef
  13. Brunner H, Northfield TC, Hofmann AF, et al. Gastric emptying and secretion of bile acids, cholesterol, and pancreatic enzymes during digestion. Duodenal perfusion studies in healthy subjects. Mayo Clin Proc. 1974;49:851-0.
  14. Dawson PA, Lan T, Rao A. Bile acid transporters. J Lipid Res. 2009;50:2340-7. CrossRef
  15. Amelsberg A, Schteingart CD, Ton-Nu HT, Hofmann AF. Carrier-mediated jejunal absorption of conjugated bile acids in the guinea pig. Gastroenterology. 1996;110:1098-06. CrossRef
  16. Oelkers P, Kirby LC, Heubi JE, Dawson PA. Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). J Clin Invest. 1997;99:1880-. CrossRef
  17. Montagnani M, Love MW, R?ssel P, et al. Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption. Scand J Gastroenterol. 2001;36:1077-0. CrossRef
  18. Ballatori N, Christian WV, Lee JY, et al. OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Hepatology. 2005;42:1270-. CrossRef
  19. Makishima M, Okamoto AY, Repa JJ, et al. Identification of a nuclear receptor for bile acids. Science. 1999;284:1362-. CrossRef
  20. Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137-4. CrossRef
  21. Inagaki T, Choi M, Moschetta A, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2005;2:217-5. CrossRef
  22. -Triantis V, Saeland E, Bijl N, et al.: Glycosylation of fibroblast growth factor receptor 4 is a key regulator of fibroblast growth factor 19-mediated down-regulation of cytochrome P450 7A1. / Hepatology 2010;52:656-6. / How Klotho-β affects the FGFR4 receptor.
  23. Kim I, Ahn SH, Inagaki T, et al. Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J Lipid Res. 2007;48:2664-2. CrossRef
  24. Lundasen T, Galman C, Angelin B, Rudling M. Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man. J Intern Med. 2006;260:530-. CrossRef
  25. -Schmidt DR, Holmstrom SR, Fon TK, et al.: Regulation of bile acid synthesis by fat-soluble vitamins A and D. / J Biol Chem 2010; 7;285:14486-4. / Recent evidence that Vitamins A and D may affect FGF15.
  26. Mekhjian HS, Phillips SF, Hofmann AF. Colonic secretion of water and electrolytes induced by bile acids: perfusion studies in man. J Clin Invest. 1971;50:1569-7. CrossRef
  27. Sun Y, Fihn BM, Sjovall H, Jodal M. Enteric neurones modulate the colonic permeability response to luminal bile acids in rat colon in vivo. Gut. 2004;53:362-. CrossRef
  28. Pedersen L, Arnfred T, Thaysen EH. Rapid screening of increased bile acid deconjugation and bile acid malabsorption by means of the glycine-l-(14?C) cholylglycine assay. Scand J Gastroenterol. 1973;8:665-2.
  29. Schiller LR, Hogan RB, Morawski SG, et al. Studies of the prevalence and significance of radiolabeled bile acid malabsorption in a group of patients with idiopathic chronic diarrhea. Gastroenterology. 1987;92:151-0.
  30. Boyd GS, Merrick MV, Monks R, Thomas IL. Se-75-labeled bile acid analogs, new radiopharmaceuticals for investigating the enterohepatic circulation. J Nucl Med. 1981;22:720-.
  31. van Tilburg AJ, de Rooij FW, van den Berg JW, van Blankenstein M. Primary bile acid diarrhoea without an ileal carrier defect: quantification of active bile acid transport across the ileal brush border membrane. Gut. 1991;32:500-. CrossRef
  32. Sinha L, Liston R, Testa HJ, Moriarty KJ. Idiopathic bile acid malabsorption: qualitative and quantitative clinical features and response to cholestyramine. Aliment Pharmacol Ther. 1998;12:839-4. CrossRef
  33. ?-Wedlake L, A'Hern R, Thomas K, et al.: Systematic review: the prevalence of idiopathic bile acid malabsorption (I-BAM) as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome (IBS). / Aliment Pharmacol Ther 2009;30:707-7. / Abnormal SeHCAT values are found in about 30% of patients with diarrhea-predominant IBS when studies containing over 1000 patients were analyzed.
  34. Sciarretta G, Vicini G, Fagioli G, et al. Use of 23-selena-25-homocholyltaurine to detect bile acid malabsorption in patients with ileal dysfunction or diarrhea. Gastroenterology. 1986;91:1-.
  35. Bajor A, Kilander A, Sjovall H, et al. The bile acid turnover rate assessed with the (75)SeHCAT test is stable in chronic diarrhoea but slightly decreased in healthy subjects after a long period of time. Dig Dis Sci. 2008;53:2935-0. CrossRef
  36. Sciarretta G, Fagioli G, Furno A, et al. 75SeHCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit. Gut. 1987;28:970-. CrossRef
  37. Smith MJ, Cherian P, Raju GS, et al. Bile acid malabsorption in persistent diarrhoea. J R Coll Physicians Lond. 2000;34:448-1.
  38. Brydon WG, Nyhlin H, Eastwood MA, Merrick MV. Serum 7 alpha-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention in the assessment of bile acid induced diarrhoea. Eur J Gastroenterol Hepatol. 1996;8:117-3. CrossRef
  39. Galman C, Arvidsson I, Angelin B, Rudling M. Monitoring hepatic cholesterol 7alpha-hydroxylase activity by assay of the stable bile acid intermediate 7alpha-hydroxy-4-cholesten-3-one in peripheral blood. J Lipid Res. 2003;44:859-6. CrossRef
  40. -Camilleri M, Nadeau A, Tremaine WJ, et al.: Measurement of serum 7alpha-hydroxy-4-cholesten-3-one (or 7alphaC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry. / Neurogastroenterol Motil 2009;21:734-e43. / Recent publication on the use of 7alphaC4 in US.
  41. Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, et al. Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function. Clin Gastroenterol Hepatol. 2010;8:159-5. CrossRef
  42. Rao AS, Wong BS, Camilleri M, et al.: Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. / Gastroenterology 2010;139:1549-8, 1558.
  43. -Wong BS, Camilleri M, Carlson PJ, et al.: A Klothobeta Variant Mediates Protein Stability and Associates with Colon Transit in Irritable Bowel Syndrome with Diarrhea. / Gastroenterology 2011;140:1934-2. / Interesting finding relating Klotho-β variants to IBS and bowel transit.
  44. Lenicek M, Duricova D, Komarek V, et al.: Bile acid malabsorption in inflammatory bowel disease: Assessment by serum markers. / Inflamm Bowel Dis 2010 epub.
  45. -Wedlake L, Thomas K, Lalji A, et al.: Effectiveness and tolerability of colesevelam hydrochloride for bile-acid malabsorption in patients with cancer: a retrospective chart review and patient questionnaire. / Clin Therap 2009;31:2549-8. / Colesevelam is effective in patients who cannot tolerate other bile acid sequestrants.
  46. Hofmann AF, Poley JR. Cholestyramine treatment of diarrhea associated with ileal resection. N Engl J Med. 1969;281:397-02. CrossRef
  47. Jung D, Fantin AC, Scheurer U, et al. Human ileal bile acid transporter gene ASBT ( / SLC10A2) is transactivated by the glucocorticoid receptor. Gut. 2004;53:78-4. CrossRef
  48. Ung KA, Gillberg R, Kilander A, Abrahamsson H. Role of bile acids and bile acid binding agents in patients with collagenous colitis. Gut. 2000;46:170-. CrossRef
  49. Fernandez-Banares F, Esteve M, Salas A, et al. Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea. Dig Dis Sci. 2001;46:2231-. CrossRef
  50. -Miehlke S, Madisch A, Bethke B, et al.: Oral budesonide for maintenance treatment of collagenous colitis: a randomized, double-blind, placebo-controlled trial. / Gastroenterology 2008;135:1510-. / Benefit of budesonide therapy in collagenous colitis which is commonly associated with bile acid malabsorption.
  51. Bajor A, Kilander A, Galman C, et al. Budesonide treatment is associated with increased bile acid absorption in collagenous colitis. Aliment Pharmacol Ther. 2006;24:1643-. CrossRef
  52. Balesaria S, Pell RJ, Abbott LJ, et al. Exploring possible mechanisms for primary bile acid malabsorption: evidence for different regulation of ileal bile acid transporter transcripts in chronic diarrhoea. Eur J Gastroenterol Hepatol. 2008;20:413-2. CrossRef
  53. Bajor A, Kilander A, Fae A, et al. Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption. Eur J Gastroenterol Hepatol. 2006;18:397-03. CrossRef
  54. Sadik R, Abrahamsson H, Ung K-A, Stotzer P-O. Accelerated regional bowel transit and overweight shown in idiopathic bile acid malabsorption. Am J Gastroenterol. 2004;99:711-. CrossRef
  55. Bajor A, Ung KA, Ohman L, et al. Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption. Acta Physiol (Oxf). 2009;197:129-7. CrossRef
  56. van Tilburg AJ, de Rooij FW, van den Berg JW, van Blankenstein M. Primary bile acid malabsorption: a pathophysiologic and clinical entity? Scand J Gastroenterol Suppl. 1992;194:66-0. CrossRef
  57. Pattni SS, Dew T, Walters JRF: A prospective study of Fibroblast Growth Factor 19 in patients with chronic diarrhoea and possible bile acid malabsorption. / Gut 2010;59 (Suppl I):A48.
  58. Miyata M, Takamatsu Y, Kuribayashi H, Yamazoe Y. Administration of ampicillin elevates hepatic primary bile acid synthesis through suppression of ileal fibroblast growth factor 15 expression. J Pharmacol Exp Ther. 2009;331:1079-5. CrossRef
  
• 作者单位：Ian Johnston (1) (2)
  Jonathan Nolan (1) (2)
  Sanjeev S. Pattni (1) (2)
  Julian R. F. Walters (1) (2)
  
  1. Section of Hepatology & Gastroenterology, Department of Medicine, Imperial College London, Du Cane Road, London, W12 0HS, UK
  2. Imperial College Healthcare, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK
  

文摘

Bile acid malabsorption occurs when there is impaired absorption of bile acids in the terminal ileum, so interrupting the normal enterohepatic circulation. The excess bile acids in the colon cause diarrhea, and treatment with bile acid sequestrants is beneficial. The condition can be diagnosed with difficulty by measuring fecal bile acids, or more easily by retention of selenohomocholyltaurine (SeHCAT), where this is available. Chronic diarrhea caused by primary bile acid diarrhea appears to be common, but is under-recognized where SeHCAT testing is not performed. Measuring excessive bile acid synthesis with 7α-hydroxy-4-cholesten-3-one may be an alternative means of diagnosis. It appears that there is no absorption defect in primary bile acid diarrhea but, instead, an overproduction of bile acids. Fibroblast growth factor 19 (FGF19) inhibits hepatic bile acid synthesis. Defective production of FGF19 from the ileum may be the cause of primary bile acid diarrhea.