Advertisement

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

  • Priya Vijayvargiya
  • Michael Camilleri
Large Intestine (B Cash, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Large Intestine

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.

Keywords

Bile acid malabsorption Microscopic colitis Inflammatory bowel disease Colonic mechanisms Fibroblast growth factor FXR agonists 

Abbreviations

ASBT

Apical sodium bile acid transporter

BA

Bile acid

BAM

Bile acid malabsorption

BAS

Bile acid sequestrants

C4

7 α-hydroxy-4-cholesten-3-one

CA

Cholic acid

CDCA

Chenodeoxycholic acid

DCA

Deoxycholic acid

FGF19

Fibroblast growth factor 19

FXR

Farsenoid X receptor

GPBAR1/TGR5

G protein coupled bile receptor 1

HAPC

High amplitude propagating contractions

IBS

C—constipation predominanat irritable bowel syndrome

IBS

D—diarrhea predominant irritable bowel syndrome

IBD

Inflammatory bowel disease

LCA

Lithocholic acid

PXR

Pregane X receptor

75SeHCAT

75Selenium homotaurocholic acid test

Notes

Compliance with Ethical Standards

Conflict of Interest

Michael Camilleri and Priya Vijayvargiya declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    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.PubMedGoogle Scholar
  2. 2.
    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.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Hofmann AF. The syndrome of ileal disease and the broken enterohepatic circulation: cholerheic enteropathy. Gastroenterology. 1967;52(4):752–7.PubMedGoogle Scholar
  4. 4.
    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.PubMedPubMedCentralGoogle Scholar
  5. 5.
    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.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Fromm H, Malavolti M. Bile acid-induced diarrhoea. Clin Gastroenterol. 1986;15(3):567–82.PubMedGoogle Scholar
  7. 7.
    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.PubMedGoogle Scholar
  8. 8.
    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.PubMedGoogle Scholar
  9. 9.
    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.PubMedGoogle Scholar
  10. 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.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Walters JR, Pattni SS. Managing bile acid diarrhoea. Ther Adv Gastroenterol. 2010;3(6):349–57.  https://doi.org/10.1177/1756283X10377126.Google Scholar
  12. 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.PubMedGoogle Scholar
  13. 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.PubMedPubMedCentralGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.Google Scholar
  16. 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.Google Scholar
  17. 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.PubMedGoogle Scholar
  18. 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. Google Scholar
  19. 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.PubMedPubMedCentralGoogle Scholar
  20. 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.PubMedPubMedCentralGoogle Scholar
  21. 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.PubMedGoogle Scholar
  22. 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. Google Scholar
  23. 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.Google Scholar
  24. 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. Google Scholar
  25. 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.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Zimmerman TW, Binder HJ. Serotonin-induced alteration of colonic electrolyte transport in the rat. Gastroenterology. 1984;86(2):310–7.PubMedGoogle Scholar
  27. 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.Google Scholar
  28. 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.PubMedGoogle Scholar
  29. 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.PubMedPubMedCentralGoogle Scholar
  30. 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.PubMedGoogle Scholar
  31. 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.PubMedPubMedCentralGoogle Scholar
  32. 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.PubMedGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 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.Google Scholar
  35. 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.PubMedPubMedCentralGoogle Scholar
  36. 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.PubMedGoogle Scholar
  37. 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.Google Scholar
  38. 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.PubMedGoogle Scholar
  39. 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.PubMedPubMedCentralGoogle Scholar
  40. 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.PubMedGoogle Scholar
  41. 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.Google Scholar
  42. 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.PubMedGoogle Scholar
  43. 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.PubMedGoogle Scholar
  44. 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.PubMedGoogle Scholar
  45. 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.PubMedGoogle Scholar
  46. 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.PubMedGoogle Scholar
  47. 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.PubMedPubMedCentralGoogle Scholar
  48. 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.PubMedGoogle Scholar
  49. 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.PubMedGoogle Scholar
  50. 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.PubMedGoogle Scholar
  51. 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.PubMedPubMedCentralGoogle Scholar
  52. 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.PubMedPubMedCentralGoogle Scholar
  53. 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.Google Scholar
  54. 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.Google Scholar
  55. 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.PubMedPubMedCentralGoogle Scholar
  56. 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.PubMedGoogle Scholar
  57. 57.
    Farahmandfar MR, Chabok M, Alade M, Bouhelal A, Patel B. Post cholecystectomy diarrhoea: a systematic review. Surg Sci. 2012;3:7.Google Scholar
  58. 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.PubMedGoogle Scholar
  59. 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.PubMedGoogle Scholar
  60. 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.PubMedGoogle Scholar
  61. 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.Google Scholar
  62. 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.Google Scholar
  63. 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.Google Scholar
  64. 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.PubMedPubMedCentralGoogle Scholar
  65. 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.PubMedGoogle Scholar
  66. 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.PubMedGoogle Scholar
  67. 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.PubMedPubMedCentralGoogle Scholar
  68. 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.Google Scholar
  69. 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.PubMedPubMedCentralGoogle Scholar
  70. 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.PubMedGoogle Scholar
  71. 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.PubMedGoogle Scholar
  72. 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.Google Scholar
  73. 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.PubMedGoogle Scholar
  74. 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.PubMedPubMedCentralGoogle Scholar
  75. 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.PubMedGoogle Scholar
  76. 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.PubMedGoogle Scholar
  77. 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. 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.PubMedGoogle Scholar
  79. 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.Google Scholar
  80. 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.Google Scholar
  81. 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. 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.PubMedGoogle Scholar
  83. 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.PubMedGoogle Scholar
  84. 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.Google Scholar
  85. 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.Google Scholar
  86. 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.PubMedGoogle Scholar
  87. 87.
    Brydon G, Ganguly R, Ghosh S. The effect of hydroxypropylcellulose on bile acid induced watery diarrhoea. Gut. 2003;52(Suppl. 1):A9.Google Scholar
  88. 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.PubMedPubMedCentralGoogle Scholar
  89. 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.Google Scholar
  90. 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.Google Scholar
  91. 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.PubMedGoogle Scholar
  92. 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.PubMedGoogle Scholar
  93. 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.PubMedGoogle Scholar
  94. 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.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Division of Gastroenterology and HepatologyMayo ClinicRochesterUSA

Personalised recommendations