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Current Gastroenterology Reports

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01-03-2018 | Large Intestine (B Cash, Section Editor)

Update on Bile Acid Malabsorption: Finally Ready for Prime Time?

Authors: Priya Vijayvargiya, Michael Camilleri

Published in: Current Gastroenterology Reports | Issue 3/2018

Abstract

Purpose of Review

To provide an update on the prevalence, pathophysiology, disease associations, and treatment options for bile acid malabsorption (BAM).

Recent Findings

•Molecular mechanisms—BAs prevent water reabsorption and increase water secretion by intracellular mediators, increasing aquaporin channels and intracellular permeability. •Inflammatory bowel disease—new molecular mechanisms of BAM are identified in patients without ileal disease, including changes in expression of ileal BA transporter and nuclear receptors involved in BA homeostasis. •Microscopic colitis—BAM is one of the mechanisms leading to microscopic colitis. •Diagnostic testing—new diagnostic tests have been launched in the USA (serum C4 and fecal 48-h BA excretion); stimulated FGF19 has higher detection of BAM compared to fasting sample alone. •Treatment—investigational FXR agonists may provide a daily, oral option for treatment of BAM instead of BA sequestrants.

Summary

There is a greater appreciation of the biological role of bile acids across multiple fields of medicine, including gastrointestinal indications.

Hofmann AF, Small DM. Detergent properties of bile salts: correlation with physiological function. Ann Rev Med. 1967;18(1):333–76. https://doi.org/10.1146/annurev.me.18.020167.002001.PubMedCrossRef

Camilleri M. Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms. J Physiol. 2014;592(14):2967–80. https://doi.org/10.1113/jphysiol.2014.270892.PubMedPubMedCentralCrossRef

Hofmann AF. The syndrome of ileal disease and the broken enterohepatic circulation: cholerheic enteropathy. Gastroenterology. 1967;52(4):752–7.PubMed

Shin A, Camilleri M, Vijayvargiya P, Busciglio I, Burton D, Ryks M, et al. Bowel functions, fecal unconjugated primary and secondary bile acids, and colonic transit in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2013;11(10):1270–5, e1. https://doi.org/10.1016/j.cgh.2013.04.020.PubMedPubMedCentralCrossRef

Wong BS, Camilleri M, Carlson P, McKinzie S, Busciglio I, Bondar O, et al. Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol. 2012;10(9):1009–15, e3. https://doi.org/10.1016/j.cgh.2012.05.006.PubMedPubMedCentralCrossRef

Fromm H, Malavolti M. Bile acid-induced diarrhoea. Clin Gastroenterol. 1986;15(3):567–82.PubMed

Scarpello JH, Hodgson E, Howlett HC. Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus. Diabetic Med. 1998;15(8):651–6. https://doi.org/10.1002/(SICI)1096-9136(199808)15:8<651::AID-DIA628>3.0.CO;2-A.PubMedCrossRef

Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio IA, et al. Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function. Clin Gastroenterol Hepatol. 2010;8(2):159–165.e5. https://doi.org/10.1016/j.cgh.2009.10.020.PubMedCrossRef

Wedlake L, A'Hern R, Russell D, Thomas K, Walters JR, Andreyev HJ. 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. 2009;30(7):707–17. https://doi.org/10.1111/j.1365-2036.2009.04081.x.PubMedCrossRef

10.

•• Bannaga A, Kelman L, O'Connor M, Pitchford C, Walters JR, Arasaradnam RP. How bad is bile acid diarrhoea: an online survey of patient-reported symptoms and outcomes. BMJ Open Gastroenterol. 2017;4(1):e000116. An online survey which evaluated the breath of symptoms association with BAM. https://doi.org/10.1136/bmjgast-2016-000116.PubMedPubMedCentralCrossRef

11.

Walters JR, Pattni SS. Managing bile acid diarrhoea. Ther Adv Gastroenterol. 2010;3(6):349–57. https://doi.org/10.1177/1756283X10377126.CrossRef

12.

Borghede MK, Schlütter JM, Agnholt JS, Christensen LA, Gormsen LC, Dahlerup JF. Bile acid malabsorption investigated by selenium-75-homocholic acid taurine (75SeHCAT) scans: causes and treatment responses to cholestyramine in 298 patients with chronic watery diarrhoea. Eur J Intern Med. 2011;22(6):e137–e40. https://doi.org/10.1016/j.ejim.2011.08.013.PubMedCrossRef

13.

Barkun AN, Love J, Gould M, Pluta H, Steinhart H. Bile acid malabsorption in chronic diarrhea: pathophysiology and treatment. Can J Gastroenterol. 2013;27(11):653–9. https://doi.org/10.1155/2013/485631.PubMedPubMedCentralCrossRef

14.

Conley DR, Coyne MJ, Bonorris GG, Chung A, Schoenfield LJ. Bile acid stimulation of colonic adenylate cyclase and secretion in the rabbit. Am J Dig Dis. 1976;21(6):453–8. https://doi.org/10.1007/BF01072128.PubMedCrossRef

15.

Ao M, Sarathy J, Domingue J, Alrefai WA, Rao MC. Chenodeoxycholic acid stimulates Cl(−) secretion via cAMP signaling and increases cystic fibrosis transmembrane conductance regulator phosphorylation in T84 cells. Am J Phys. 2013;305(4):C447–56. https://doi.org/10.1152/ajpcell.00416.2012.CrossRef

16.

Domingue JC, Ao M, Sarathy J, Rao MC. Chenodeoxycholic acid requires activation of EGFR, EPAC, and Ca2+ to stimulate CFTR-dependent Cl- secretion in human colonic T84 cells. Am J Phys. 2016;311(5):C777–92. https://doi.org/10.1152/ajpcell.00168.2016.CrossRef

17.

Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M, et al. A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003;278(11):9435–40. https://doi.org/10.1074/jbc.M209706200.PubMedCrossRef

18.

•• Borg JF, Yde J, Wu Q, Lajczak N, Keely S, Fenton RA, et al. Regulated expression of the Na+/K+-ATPase pump in colonic epithelium by bile acids. FASEB J. 2017;31(Suppl. 1):856. 10-10. This study details that another mechanism diarrhea in patient s with BAM is the lack of electrolyte and water absorption because of changes in the basolateral sodium/potassium ATPase channels.

19.

Suhail M. Na(+), K(+)-ATPase: ubiquitous multifunctional transmembrane protein and its relevance to various pathophysiological conditions. J Clin Med Res. 2010;2(1):1–17. https://doi.org/10.4021/jocmr2010.02.263w.PubMedPubMedCentralCrossRef

20.

Cipriani S, Mencarelli A, Chini MG, Distrutti E, Renga B, Bifulco G, et al. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS One. 2011;6(10):e25637. https://doi.org/10.1371/journal.pone.0025637.PubMedPubMedCentralCrossRef

21.

Chadwick VS, Gaginella TS, Carlson GL, Debongnie JC, Phillips SF, Hofmann AF. Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon. J Lab Clin Med. 1979;94(5):661–74.PubMed

22.

• Keely SJ, Scharl MM, Bertelsen LS, Hagey LR, Barrett KE, Hofmann AF. Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: structure-activity relationships. Am J Phys. 2007;292:G290–7. This study describes the mechanism of colonic chloride and water secretion in the setting of BAM.

23.

•• Sarathy J, Detloff SJ, Ao M, Khan N, French S, Sirajuddin H, et al. The Yin and Yang of bile acid action on tight junctions in a model colonic epithelium. Physiologic Rep. 2017;5(10):e13294. This paper discusses methods of increased water secretion into the colon via decrease in tight junction and increased paracellular movement and an increase in aquaporin channels. https://doi.org/10.14814/phy2.13294.CrossRef

24.

•• Yde J, Borg J, Fenton RA, Moeller HB. Altered expression of aquaporin water channels in a rat model of chronic diarrhea due to bile acid malabsorption. FASEB J. 2017;31(Suppl. 1):703. 14-14. This paper discusses methods of increased water secretion into the colon via decrease in tight junction and increased paracellular movement and an increase in aquaporin channels.

25.

Ma T, Verkman AS. Aquaporin water channels in gastrointestinal physiology. J Physiol. 1999;517(Pt 2):317–26. https://doi.org/10.1111/j.1469-7793.1999.0317t.x.PubMedPubMedCentralCrossRef

26.

Zimmerman TW, Binder HJ. Serotonin-induced alteration of colonic electrolyte transport in the rat. Gastroenterology. 1984;86(2):310–7.PubMed

27.

Bardhan PK, Rahman AS, Islam S, Rahman M, Gyr K. Effects of tropisetron, a 5-hydroxytryptamine type 3 receptor blocker, on intestinal secretion induced by cholera toxin or deoxycholic acid in rabbits in vivo. J Intl Med Res. 1993;21(6):323–33. https://doi.org/10.1177/030006059302100603.CrossRef

28.

Camilleri M, Murphy R, Chadwick VS. Pharmacological inhibition of chenodeoxycholate-induced fluid and mucus secretion and mucosal injury in the rabbit colon. Dig Dis Sci. 1982;27(10):865–9. https://doi.org/10.1007/BF01316567.PubMedCrossRef

29.

Duboc H, Tolstanova G, Yuan PQ, Wu V, Kaji I, Biraud M, et al. Reduction of epithelial secretion in male rat distal colonic mucosa by bile acid receptor TGR5 agonist, INT-777: role of submucosal neurons. Neurogastroenterol Motil. 2016;28(11):1663–76. https://doi.org/10.1111/nmo.12866.PubMedPubMedCentralCrossRef

30.

Ward JB, Mroz MS, Keely SJ. The bile acid receptor, TGR5, regulates basal and cholinergic-induced secretory responses in rat colon. Neurogastroenterol Motil. 2013;25(8):708–11. https://doi.org/10.1111/nmo.12148.PubMedCrossRef

31.

• Bunnett NW. Neuro-humoral signalling by bile acids and the TGR5 receptor in the gastrointestinal tract. J Physiol. 2014;592(14):2943–50. This paper identifies that BAs target the TGR5 receptors which activate colonic motility and directly on the enteric neurons. https://doi.org/10.1113/jphysiol.2014.271155.PubMedPubMedCentralCrossRef

32.

Mekhjian HS, Phillips SF, Hofmann AF. Colonic absorption of unconjugated bile acids: perfusion studies in man. Dig Dis Sci. 1979;24(7):545–50. https://doi.org/10.1007/BF01489324.PubMedCrossRef

33.

Alemi F, Poole DP, Chiu J, Schoonjans K, Cattaruzza F, Grider JR, et al. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology. 2013;144(1):145–54. https://doi.org/10.1053/j.gastro.2012.09.055.PubMedCrossRef

34.

Bampton PA, Dinning PG, Kennedy ML, Lubowski DZ, Cook IJ. The proximal colonic motor response to rectal mechanical and chemical stimulation. Am J Phys. 2002;282(3):G443–9.

35.

Rao AS, Wong BS, Camilleri M, Odunsi-Shiyanbade ST, McKinzie S, Ryks M, et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology. 2010;139(5):1549–58, e1. https://doi.org/10.1053/j.gastro.2010.07.052.PubMedPubMedCentralCrossRef

36.

Dior M, Delagrèverie H, Duboc H, Jouet P, Coffin B, Brot L, et al. Interplay between bile acid metabolism and microbiota in irritable bowel syndrome. Neurogastroenterol Motil. 2016;28(9):1330–40. https://doi.org/10.1111/nmo.12829.PubMedCrossRef

37.

Ward JBJ, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ni Gabhann J, et al. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Phys. 2017;312:G550–8.CrossRef

38.

Biagioli M, Carino A, Cipriani S, Francisci D, Marchiano S, Scarpelli P, et al. The bile acid receptor GPBAR1 regulates the M1/M2 phenotype of intestinal macrophages and activation of GPBAR1 rescues mice from murine colitis. J Immunol. 2017;199(2):718–33. https://doi.org/10.4049/jimmunol.1700183.PubMedCrossRef

39.

Yoneno K, Hisamatsu T, Shimamura K, Kamada N, Ichikawa R, Kitazume MT, et al. TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn’s disease. Immunology. 2013;139(1):19–29. https://doi.org/10.1111/imm.12045.PubMedPubMedCentralCrossRef

40.

Ji CG, Xie XL, Yin J, Qi W, Chen L, Bai Y, et al. Bile acid receptor TGR5 overexpression is associated with decreased intestinal mucosal injury and epithelial cell proliferation in obstructive jaundice. Transl Res. 2017;182:88–102. https://doi.org/10.1016/j.trsl.2016.12.001.PubMedCrossRef

41.

Svane MS, Bojsen-Moller KN, Madsbad S, Holst JJ. Updates in weight loss surgery and gastrointestinal peptides. Curr Opin Endocrinol Diab Obes. 2015;22(1):21–8. https://doi.org/10.1097/MED.0000000000000131.CrossRef

42.

Hofmann AF, Poley JR. Cholestyramine treatment of diarrhea associated with ileal resection. N Engl J Med. 1969;281(8):397–402. https://doi.org/10.1056/NEJM196908212810801.PubMedCrossRef

43.

Akerlund JE, Reihner E, Angelin B, Rudling M, Ewerth S, Bjorkhem I, et al. Hepatic metabolism of cholesterol in Crohn’s disease. Effect of partial resection of ileum. Gastroenterology. 1991;100(4):1046–53. https://doi.org/10.1016/0016-5085(91)90281-O.PubMedCrossRef

44.

Hofmann AF, Poley JR. 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. 1972;62(5):918–34.PubMed

45.

Davie RJ, Hosie KB, Grobler SP, Newbury-Ecob RA, Keighley MRB, Birch NJ. Ileal bile acid malabsorption in colonic Crohn’s disease. Br J Surg. 1994;81(2):289–90. https://doi.org/10.1002/bjs.1800810246.PubMedCrossRef

46.

Jahnel J, Fickert P, Hauer AC, Hogenauer C, Avian A, Trauner M. Inflammatory bowel disease alters intestinal bile acid transporter expression. Drug Metab Dispos. 2014;42(9):1423–31. https://doi.org/10.1124/dmd.114.058065.PubMedCrossRef

47.

•• Jung D, Fantin AC, Scheurer U, Fried M, Kullak-Ublick GA. Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor. Gut. 2004;53(1):78–84. This study details the unique finding of decreased transcription of the ASBT receptor in patients with Crohn’s disease, identifying a new pathway of BAM in patients without overt ileal disease. https://doi.org/10.1136/gut.53.1.78.PubMedPubMedCentralCrossRef

48.

• Iwamoto J, Saito Y, Honda A, Miyazaki T, Ikegami T, Matsuzaki Y. Bile acid malabsorption deactivates pregnane X receptor in patients with Crohn’s disease. Inflamm Bowel Dis. 2013;19(6):1278–84. PXR is important in regulating hepatic BA and intestinal inflammation. In Crohn’s disease patients who have BAM, PXR may be low and can result in diarrhea with mucosal inflammation without evidence of active Crohn’s disease. https://doi.org/10.1097/MIB.0b013e318281f423.PubMedCrossRef

49.

Dring MM, Goulding CA, Trimble VI, Keegan D, Ryan AW, Brophy KM, et al. The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease. Gastroenterology. 2006;130(2):341–8; quiz 592. https://doi.org/10.1053/j.gastro.2005.12.008.PubMedCrossRef

50.

Prantera C, Lochs H, Campieri M, Scribano ML, Sturniolo GC, Castiglione F, et al. Antibiotic treatment of Crohn’s disease: results of a multicentre, double blind, randomized, placebo-controlled trial with rifaximin. Aliment Pharmacol Ther. 2006;23(8):1117–25. https://doi.org/10.1111/j.1365-2036.2006.02879.x.PubMedCrossRef

51.

Cheng J, Shah YM, Ma X, Pang X, Tanaka T, Kodama T, et al. Therapeutic role of rifaximin in inflammatory bowel disease: clinical implication of human pregnane X receptor activation. J Pharmacol Exp Ther. 2010;335(1):32–41. https://doi.org/10.1124/jpet.110.170225.PubMedPubMedCentralCrossRef

52.

Stacey R, Green JT. Radiation-induced small bowel disease: latest developments and clinical guidance. Ther Adv Chronic Dis. 2014;5(1):15–29. https://doi.org/10.1177/2040622313510730.PubMedPubMedCentralCrossRef

53.

White KL, Henson CC, Jenner K, Burden S, Lal S, Davidson SE, et al. PTH-247 Modern pelvic chemoradiotherapy techniques continue to cause bile acid malabsorption. Gut. 2015;64(Suppl 1):A519.

54.

Phillips F, Muls A, Lalji A, Andreyev H. Are bile acid malabsorption and bile acid diarrhoea important causes of loose stool complicating cancer therapy? Colorect Dis. 2015;17(8):730–4. https://doi.org/10.1111/codi.12932.CrossRef

55.

Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood. 2006;108(10):3458–64. https://doi.org/10.1182/blood-2006-04-015909.PubMedPubMedCentralCrossRef

56.

Pawlyn C, Khan MS, Muls A, Sriskandarajah P, Kaiser MF, Davies FE, et al. Lenalidomide-induced diarrhea in patients with myeloma is caused by bile acid malabsorption that responds to treatment. Blood. 2014;124(15):2467–8. https://doi.org/10.1182/blood-2014-06-583302.PubMedCrossRef

57.

Farahmandfar MR, Chabok M, Alade M, Bouhelal A, Patel B. Post cholecystectomy diarrhoea: a systematic review. Surg Sci. 2012;3:7.CrossRef

58.

• Yueh T-P, Chen F-Y, Lin T-E, Chuang M-T. Diarrhea after laparoscopic cholecystectomy: associated factors and predictors. Asian J Surg. 2014;37(4):171–7. Rates of BAM in post-cholecystecomy patients are lower than previously expected with rates decreasing as patient’s get further from their surgical date. https://doi.org/10.1016/j.asjsur.2014.01.008.PubMedCrossRef

59.

Walters JR, Tasleem AM, Omer OS, Brydon WG, Dew T, le Roux CW. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol. 2009;7(11):1189–94. https://doi.org/10.1016/j.cgh.2009.04.024.PubMedCrossRef

60.

Johnston IM, Nolan JD, Pattni SS, Appleby RN, Zhang JH, Kennie SL, et al. Characterizing factors associated with differences in FGF19 blood levels and synthesis in patients with primary bile acid diarrhea. Am J Gastroenterol. 2016;111(3):423–32. https://doi.org/10.1038/ajg.2015.424.PubMedCrossRef

61.

Camilleri M, Shin A, Busciglio I, Carlson P, Acosta A, Bharucha AE, et al. Genetic variation in GPBAR1 predisposes to quantitative changes in colonic transit and bile acid excretion. Am J Phys. 2014;307:G508–16.CrossRef

62.

Camilleri M, Klee EW, Shin A, Carlson P, Li Y, Grover M, et al. Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit. Am J Phys. 2014;306:G13–26.

63.

Einarsson K, Eusufzai S, Johansson U, Lofberg R, Theodorsson E, Veress B. Villous atrophy of distal ileum and lymphocytic colitis in a woman with bile acid malabsorption. Eur J Gastroenterol Hepatol. 1992;4:585–90.

64.

Marteau P, Lavergne-Slove A, Lemann M, Bouhnik Y, Bertheau P, Becheur H, et al. Primary ileal villous atrophy is often associated with microscopic colitis. Gut. 1997;41(4):561–4. https://doi.org/10.1136/gut.41.4.561.PubMedPubMedCentralCrossRef

65.

Fernandez-Banares F, Esteve M, Salas A, Forne TM, Espinos JC, Martin-Comin J, et al. Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea. Dig Dis Sci. 2001;46(10):2231–8. https://doi.org/10.1023/A:1011927302076.PubMedCrossRef

66.

Giardiello FM, Bayless TM, Jessurun J, Hamilton SR, Yardley JH. Collagenous colitis: physiologic and histopathologic studies in seven patients. Ann Intern Med. 1987;106(1):46–9. https://doi.org/10.7326/0003-4819-106-1-46.PubMedCrossRef

67.

Kingham JG, Levison DA, Ball JA, Dawson AM. Microscopic colitis-a cause of chronic watery diarrhoea. BMJ. 1982;285(6355):1601–4. https://doi.org/10.1136/bmj.285.6355.1601.PubMedPubMedCentralCrossRef

68.

Eusufzai S, Löfberg R, Veress B, Einarsson K, Angelin B. Studies on bile acid metabolism in colagenous colitis: no evidence of bile acid malabsorption as determined by the SeHCAT test. Eur J Gastroenterol Hepatol. 1992;4:317–21.

69.

Ung K, Gillberg R, Kilander A, Abrahamsson H. Role of bile acids and bile acid binding agents in patients with collagenous colitis. Gut. 2000;46(2):170–5. https://doi.org/10.1136/gut.46.2.170.PubMedPubMedCentralCrossRef

70.

Galatola G, Jazrawi RP, Bridges C, Joseph AE, Northfield TC. Direct measurement of first-pass ileal clearance of a bile acid in humans. Gastroenterology. 1991;100(4):1100–5. https://doi.org/10.1016/0016-5085(91)90288-V.PubMedCrossRef

71.

Brunner H, Northfield T, Hofmann A, Go V, Summerskill WH. Gastric emptying and secretion of bile acids, cholesterol, and pancreatic enzymes during digestion: duodenal perfusion studies in healthy subjects. Mayo Clin Proc. 1974;49(11):851–60.PubMed

72.

Peters AM, Walters JR. Recycling rate of bile acids in the enterohepatic recirculation as a major determinant of whole body 75SeHCAT retention. Eur J Nucl Med Molecul Imag. 2013;40(10):1618–21. https://doi.org/10.1007/s00259-013-2466-z.CrossRef

73.

Scheurlen C, Kruis W, Bull U, Stellaard F, Lang P, Paumgartner G. Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders. Digestion. 1986;35(2):102–8. https://doi.org/10.1159/000199353.PubMedCrossRef

74.

Sciarretta G, Fagioli G, Furno A, Vicini G, Cecchetti L, Grigolo B, et al. 75Se HCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit. Gut. 1987;28(8):970–5. https://doi.org/10.1136/gut.28.8.970.PubMedPubMedCentralCrossRef

75.

•• Peleman C, Camilleri M, Busciglio I, Burton D, Donato L, Zinsmeister AR. Colonic transit and bile acid synthesis or excretion in patients with irritable bowel syndrome–diarrhea without bile acid malabsorption. Clin Gastroenterol Hepatol. 2017;15(5):720–7, e1. This paper describes that the increased presence of primary bile acids may be sufficient to increase colonic transit. This may support diagnosis of BAM in patients with total fecal BA < 2,337μmol/48h but have a high proportion of primary fecal BAs or secretory BAs. https://doi.org/10.1016/j.cgh.2016.11.012.PubMedCrossRef

76.

Sauter GH, Munzing W, Ritter CV, Paumgartner G. Bile acid malabsorption as a cause of chronic diarrhea diagnostic value of 7α-hydroxy-4-cholesten-3-one in serum. Dig Dis Sci. 1999;44(1):14–9. https://doi.org/10.1023/A:1026681512303.PubMedCrossRef

77.

Donato LJ, Lueke A, Kenyon SM, Meeusen JW, Camilleri M. Description of analytical method and clinical utility of measuring serum 7-alpha-hydroxy-4-cholesten-3-one (7aC4) by mass spectrometry. Clin Biochem. 2017; https://doi.org/10.1016/j.clinbiochem.2017.10.008.

78.

Vijayvargiya P, Camilleri M, Carlson P, Lueke A, O'Neill J, Burton D, et al. Performance characteristics of serum C4 and FGF19 measurements to exclude the diagnosis of bile acid diarrhoea in IBS-diarrhoea and functional diarrhoea. Aliment Pharmacol Ther. 2017;46(6):581–8. https://doi.org/10.1111/apt.14214.PubMedCrossRefPubMedCentral

79.

Gothe F, Beigel F, Rust C, Hajji M, Koletzko S, Freudenberg F. Bile acid malabsorption assessed by 7 alpha-hydroxy-4-cholesten-3-one in pediatric inflammatory bowel disease: correlation to clinical and laboratory findings. J Crohn's & Colitis. 2014;8(9):1072–8. https://doi.org/10.1016/j.crohns.2014.02.027.CrossRef

80.

Zhang JH, Nolan JD, Kennie SL, Johnston IM, Dew T, Dixon PH, et al. Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids. Am J Phys. 2013;304:G940–8.

81.

Vijayvargiya P, Busciglio I, Burton D, Donato L, Lueke A, Camilleri M. Bile acid deficiency in a subgroup of patients with irritable bowel syndrome with constipation based on biomarkers in serum and fecal samples. Clin Gastroenterol Hepatol. 2017; https://doi.org/10.1016/j.cgh.2017.06.039.

82.

Borup C, Syversen C, Bouchelouche P, Damgaard M, Graff J, Rumessen JJ, et al. Diagnosis of bile acid diarrhoea by fasting and postprandial measurements of fibroblast growth factor 19. Eur J Gastroenterol Hepatol. 2015;27(12):1399–402. https://doi.org/10.1097/MEG.0000000000000476.PubMedCrossRef

83.

•• Borup C, Wildt S, Rumessen JJ, Bouchelouche PN, Graff J, Damgaard M, et al. Chenodeoxycholic acid stimulated fibroblast growth factor 19 response - a potential biochemical test for bile acid diarrhoea. Aliment Pharmacol Ther. 2017;45(11):1433–42. This study demonstrated that stimulated FGF19 may be a better marker of diagnosing BAM. Patients with BAM will not have a significant increase in FGF19 post meal + CDCA as compared to healthy controls. https://doi.org/10.1111/apt.14056.PubMedCrossRef

84.

Jackson A, Lalji A, Kabir M, Muls A, Gee C, Vyoral S, et al. PTU-128 The efficacy of using low-fat dietary interventions to manage bile acid malabsorption. Gut. 2017;66(Suppl.2):A114.

85.

Beigel F, Teich N, Howaldt S, Lammert F, Maul J, Breiteneicher S, et al. Colesevelam for the treatment of bile acid malabsorption-associated diarrhea in patients with Crohn’s disease: a randomized, double-blind, placebo-controlled study. J Crohn's & Colitis. 2014;8(11):1471–9. https://doi.org/10.1016/j.crohns.2014.05.009.CrossRef

86.

Fernandez-Banares F, Rosinach M, Piqueras M, Ruiz-Cerulla A, Modolell I, Zabana Y, et al. Randomised clinical trial: colestyramine vs. hydroxypropyl cellulose in patients with functional chronic watery diarrhoea. Aliment Pharmacol Ther. 2015;41(11):1132–40. https://doi.org/10.1111/apt.13193.PubMedCrossRef

87.

Brydon G, Ganguly R, Ghosh S. The effect of hydroxypropylcellulose on bile acid induced watery diarrhoea. Gut. 2003;52(Suppl. 1):A9.

88.

Camilleri M, Acosta A, Busciglio I, Boldingh A, Dyer RB, Zinsmeister AR, et al. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2015;41(5):438–48. https://doi.org/10.1111/apt.13065.PubMedPubMedCentralCrossRef

89.

Orekoya O, McLaughlin J, Leitao E, Johns W, Lal S, Paine P. Quantifying bile acid malabsorption helps predict response and tailor sequestrant therapy. Clin Med. 2015;15(3):252–7. https://doi.org/10.7861/clinmedicine.15-3-252.CrossRef

90.

Pellicciari R, Costantino G, Camaioni E, Sadeghpour BM, Entrena A, Willson TM, et al. Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid. J Medicinal Chem. 2004;47(18):4559–69. https://doi.org/10.1021/jm049904b.CrossRef

91.

Mroz MS, Keating N, Ward JB, Sarker R, Amu S, Aviello G, et al. Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo. Gut. 2014;63(5):808–17. https://doi.org/10.1136/gutjnl-2013-305088.PubMedCrossRef

92.

Walters J, Johnston I, Nolan J, Vassie C, Pruzanski M, Shapiro D. The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid. Aliment Pharmacol Ther. 2015;41(1):54–64. https://doi.org/10.1111/apt.12999.PubMedCrossRef

93.

Baghdasaryan A, Fuchs CD, Österreicher CH, Lemberger UJ, Halilbasic E, Påhlman I, et al. Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis. J Hepatol. 2016;64(3):674–81. https://doi.org/10.1016/j.jhep.2015.10.024.PubMedCrossRef

94.

Ajouz H, Mukherji D, Shamseddine A. Secondary bile acids: an underrecognized cause of colon cancer. World J Surg Oncol. 2014;12(1):164. https://doi.org/10.1186/1477-7819-12-164.PubMedPubMedCentralCrossRef

Title: Update on Bile Acid Malabsorption: Finally Ready for Prime Time?
Authors: Priya Vijayvargiya
Michael Camilleri
Publication date: 01-03-2018
Publisher: Springer US
Published in: Current Gastroenterology Reports / Issue 3/2018
Print ISSN: 1522-8037
Electronic ISSN: 1534-312X
DOI: https://doi.org/10.1007/s11894-018-0615-z

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Abstract

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ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page