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Bile Acid Diarrhea: Prevalence, Pathogenesis, and Therapy

Michael Camilleri
거트앤리버 소화기연관학회협의회|2015.05|Gut and Liver|제9권 제3호|pp. 332-339

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키워드

C4CYP7A1MalabsorptionFXRFGF-19Klotho b

초록

Bile acid diarrhea (BAD) is usually seen in patients with ileal Crohn’s disease or ileal resection. However, 25% to 50% of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) also have evidence of BAD. It is estimated that 1% of the population may have BAD. The causes of BAD include a deficiency in fibroblast growth factor 19 (FGF-19), a hormone produced in enterocytes that regulates hepatic bile acid (BA) synthesis. Other potential causes include genetic variations that affect the proteins involved in BA enterohepatic circulation and synthesis or in the TGR5 receptor that mediates the actions of BA in colonic secretion and motility. BAs enhance mucosal permeability, induce water and electrolyte secretion, and accelerate colonic transit partly by stimulating propulsive high-amplitude colonic contractions. There is an increased proportion of primary BAs in the stool of patients with IBS-D, and some changes in the fecal microbiome have been described. There are several methods of diagnosing BAD, such as 75selenium homotaurocholic acid test retention, serum C4, FGF-19, and fecal BA measurement; presently, therapeutic trials with BA sequestrants are most commonly used for diagnosis. Management involves the use of BA sequestrants including cholestyramine, colestipol, and colesevelam. FXR agonists such as obeticholic acid constitute a promising new approach to treating BAD.

Abstract

Bile acid diarrhea (BAD) is usually seen in patients with ileal Crohn’s disease or ileal resection. However, 25% to 50% of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) also have evidence of BAD. It is estimated that 1% of the population may have BAD. The causes of BAD include a deficiency in fibroblast growth factor 19 (FGF-19), a hormone produced in enterocytes that regulates hepatic bile acid (BA) synthesis. Other potential causes include genetic variations that affect the proteins involved in BA enterohepatic circulation and synthesis or in the TGR5 receptor that mediates the actions of BA in colonic secretion and motility. BAs enhance mucosal permeability, induce water and electrolyte secretion, and accelerate colonic transit partly by stimulating propulsive high-amplitude colonic contractions. There is an increased proportion of primary BAs in the stool of patients with IBS-D, and some changes in the fecal microbiome have been described. There are several methods of diagnosing BAD, such as 75selenium homotaurocholic acid test retention, serum C4, FGF-19, and fecal BA measurement; presently, therapeutic trials with BA sequestrants are most commonly used for diagnosis. Management involves the use of BA sequestrants including cholestyramine, colestipol, and colesevelam. FXR agonists such as obeticholic acid constitute a promising new approach to treating BAD.

참고문헌 (66)

  1. Hofmann AF, "Detergent properties of bile salts: correlation with physiological function", Annu Rev Med, 18, pp.333~376 (1967)
  2. Ridlon JM, "Bile salt biotransformations by human intestinal bacteria", J Lipid Res, 47, pp.241~259 (2006)
  3. Hofmann AF, "The syndrome of ileal disease and the broken enterohepatic circulation: cholerhetic enteropathy", Gastroenterology, 52, pp.752~757 (1967)
  4. Caspary WF, "Alteration of bile acid metabolism and vitamin-B12-absorption in diabetics on biguanides", Diabetologia, 13, pp.187~193 (1977)
  5. Scarpello JH, "Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus", Diabet Med, 15, pp.651~656 (1998)
  6. Miles JM, "Effects of metformin on bile acid metabolism in type 2 diabetes", Diabetes, 63(1), pp.A285~A286 (2014)
  7. Camilleri M, "Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms", J Physiol, 592, pp.2967~2980 (2014)
  8. Lundåsen T, "Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man", J Intern Med, 260, pp.530~536 (2006)
  9. Walters JR, "A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis", Clin Gastroenterol Hepatol, 7, pp.1189~1194 (2009)
  10. Wong BS, "Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea", Clin Gastroenterol Hepatol, 10, pp.1009~1015 (2012)
  11. Rao AS, "Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis", Gastroenterology, 139, pp.1549~1558 (2010)
  12. Montagnani M, "Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption", Scand J Gastroenterol, 36, pp.1077~1080 (2001)
  13. Montagnani M, "Analysis of ileal sodium", bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption, 2006, pp.12, 7710~7714
  14. Bajor A, "Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption", Eur J Gastroenterol Hepatol, 18, pp.397~403 (2006)
  15. Sadik R, "Accelerated regional bowel transit and overweight shown in idiopathic bile acid malabsorption", Am J Gastroenterol, 99, pp.711~718 (2004)
  16. Valdés Olmos R, "Effect of loperamide and delay of bowel motility on bile acid malabsorption caused by late radiation damage and ileal resection", Eur J Nucl Med, 18, pp.346~350 (1991)
  17. Yeoh EK, "Gastrointestinal function in chronic radiation enteritis: effects of loperamide-N-oxide", Gut, 34, pp.476~482 (1993)
  18. Wong BS, "A Klothob variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea", Gastroenterology, 140, pp.1934~1942 (2011)
  19. Camilleri M, "Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit", Am J Physiol Gastrointest Liver Physiol, 306, pp.G13~G26 (2014)
  20. Kawamata Y, "A G protein-coupled receptor responsive to bile acids", J Biol Chem, 278, pp.9435~9440 (2003)
  21. Ward JB, "The bile acid receptor, TGR5, regulates basal and cholinergic-induced secretory responses in rat colon", Neurogastroenterol Motil, 25, pp.708~711 (2013)
  22. Poole DP, "Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system", Neurogastroenterol Motil, 22, pp.814~825 (2010)
  23. Alemi F, "The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice", Gastroenterology, 144, pp.145~154 (2013)
  24. Camilleri M, "Genetic variation in GPBAR1 predisposes to quantitative changes in colonic transit and bile acid excretion", Am J Physiol Gastrointest Liver Physiol, 307, pp.G508~G516 (2014)
  25. Bunnett NW, "Neuro-humoral signalling by bile acids and the TGR5 receptor in the gastrointestinal tract", J Physiol, 592, pp.2943~2950 (2014)
  26. Chadwick VS, "Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon", J Lab Clin Med, 94, pp.661~674 (1979)
  27. Conley DR, "Bile acid stimulation of colonic adenylate cyclase and secretion in the rabbit", Am J Dig Dis, 21, pp.453~458 (1976)
  28. Ao M, "Chenodeoxycholic acid stimulates Cl(-) secretion via cAMP signaling and increases cystic fibrosis transmembrane conductance regulator phosphorylation in T84 cells", Am J Physiol Cell Physiol, 305, pp.C447~C456 (2013)
  29. Alrefai WA, "Taurodeoxycholate modulates apical Cl-", OH- exchange activity in Caco2 cells, 2007, pp.52, 1270~1278
  30. Camilleri M, "Dose-related effects of chenodeoxycholic acid in the rabbit colon", Dig Dis Sci, 25, pp.433~438 (1980)
  31. Barcelo A, "Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon", Dig Dis Sci, 46, pp.1223~1231 (2001)
  32. Bampton PA, "The proximal colonic motor response to rectal mechanical and chemical stimulation", Am J Physiol Gastrointest Liver Physiol, 282, pp.G443~F449 (2002)
  33. Hofmann AF, "Cholestyramine treatment of diarrhea associated with ileal resection", N Engl J Med, 281, pp.397~402 (1969)
  34. Hofmann AF, "Role of bile acid malabsorption in pathogenesis of diarrhea and steatorrhea in patients with ileal resection. I. Response to cholestyramine or replacement of dietary long chain triglyceride by medium chain triglyceride", Gastroenterology, 62, pp.918~934 (1972)
  35. Poley JR, "Role of fat maldigestion in pathogenesis of steatorrhea in ileal resection. Fat digestion after two sequential test meals with and without cholestyramine", Gastroenterology, 71, pp.38~44 (1976)
  36. Wedlake L, "Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome", Aliment Pharmacol Ther, 30, pp.707~717 (2009)
  37. Gracie DJ, "Prevalence of, and predictors of, bile acid malabsorption in outpatients with chronic diarrhea", Neurogastroenterol Motil, 24, pp.983~e538 (2012)
  38. Shin A, "Bowel functions, fecal unconjugated primary and secondary bile acids, and colonic transit in patients with irritable bowel syndrome", Clin Gastroenterol Hepatol, 11, pp.1270~1275 (2013)
  39. Walters JR, "Managing bile acid diarrhoea", Therap Adv Gastroenterol, 3, pp.349~357 (2010)
  40. Sayin SI, "Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist", Cell Metab, 17, pp.225~235 (2013)
  41. Zhao Y, "Gut microbiota composition modifies fecal metabolic profiles in mice", J Proteome Res, 12, pp.2987~2999 (2013)
  42. Ridlon JM, "Cirrhosis, bile acids and gut microbiota: unraveling a complex relationship", Gut Microbes, 4, pp.382~387 (2013)
  43. Ou J, "Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans", Am J Clin Nutr, 98, pp.111~120 (2013)
  44. Duboc H, "Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases", Gut, 62, pp.531~539 (2013)
  45. Duboc H, "Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome", Neurogastroenterol Motil, 24, pp.513~520 (2012)
  46. Camilleri M, "Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea", Am J Gastroenterol, 109, pp.1621~1630 (2014)
  47. Vijayvargiya P, "Methods for diagnosis of bile acid malabsorption in clinical practice", Clin Gastroenterol Hepatol, 11, pp.1232~1239 (2013)
  48. Fromm H, "Breath test for altered bile-acid metabolism", Lancet, 2, pp.621~625 (1971)
  49. Thaysen EH, "Assessment of ileal function by abdominal counting of the retention of a gamma emitting bile acid analogue", Gut, 23, pp.862~865 (1982)
  50. Williams AJ, "Idiopathic bile acid malabsorption: a review of clinical presentation, diagnosis, and response to treatment", Gut, 32, pp.1004~1006 (1991)
  51. Gälman C, "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, 44, pp.859~866 (2003)
  52. Camilleri M, "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, 21, pp.734~ (2009)
  53. Sauter GH, "Bile acid malabsorption as a cause of chronic diarrhea: diagnostic value of 7alpha-hydroxy-4-cholesten-3-one in serum", Dig Dis Sci, 44, pp.14~19 (1999)
  54. Camilleri M, "Validating biomarkers of treatable mechanisms in irritable bowel syndrome", Neurogastroenterol Motil, 26, pp.1677~1685 (2014)
  55. Pattni SS, "Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention", Aliment Pharmacol Ther, 38, pp.967~976 (2013)
  56. Pattni SS, "Fibroblast growth factor 19 and 7alpha-hydroxy-4-cholesten-3-one in the diagnosis of patients with possible bile acid diarrhea", Clin Transl Gastroenterol, 3, pp.e18~ (2012)
  57. Covington JA, "Application of a novel tool for diagnosing bile acid diarrhoea", Sensors, 13, pp.11899~11912 (2013)
  58. Wilson AD, "Advances in electronic-nose technologies developed for biomedical applications", Sensors, 11, pp.1105~1176 (2011)
  59. Arasaradnam RP, "Evaluation of gut bacterial populations using an electronic e-nose and field asymmetric ion mobility spectrometry: further insights into ‘fermentonomics’", J Med Eng Technol, 36, pp.333~337 (2012)
  60. Halilbasic E, "Bile acid transporters and regulatory nuclear receptors in the liver and beyond", J Hepatol, 58, pp.155~168 (2013)
  61. Stotzer PO, "Effect of cholestyramine on gastrointestinal transit in patients with idiopathic bile acid diarrhea: a prospective, open-label study", Neuroenterology, 2 (2013)
  62. Bajor A, "Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS", Gut, 64, pp.84~92 (2015)
  63. Odunsi-Shiyanbade ST, "Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function", Clin Gastroenterol Hepatol, 8, pp.159~165 (2010)
  64. Zhang JH, "Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids", Am J Physiol Gastrointest Liver Physiol, 304, pp.G940~G948 (2013)
  65. Johnston IM, "A new therapy for chronic diarrhea? A proof of concept study of the FXR agonist obeticholic acid in patients with primary bile acid diarrhea", Gastroenterology, 144(1), pp.60~ (2013)
  66. Mroz MS, "Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo", Gut, 63, pp.808~817 (2014)

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