The role of bile acids in the pathogenesis of bowel diseases

COMMENTARY ON THE LAW

The role of bile acids in the pathogenesis of bowel diseases

Magdalena Panek-Jeziorna 1 , Agata Mulak 1

1. Katedra i Klinika Gastroenterologii i Hepatologii, Uniwersytet Medyczny we Wrocławiu

Published: 2017-08-24
DOI: 10.5604/01.3001.0010.3852
GICID: 01.3001.0010.3852
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2017; 71 : 737-746

 

Abstract

Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors. Genetic factors associated with the regulation of bile acid synthesis, transport and action may significantly influence gastrointestinal function and predispose to diarrhea resulting from bile acid malabsorption. Methods used in the diagnosis of bile acid malabsorption include 75selenium-homotaurocholic acid test, serum C4 and fibroblast growth factor 19 (FGF19), as well as fecal bile acid levels. The paper presents the latest data on the role of bile acid in the pathogenesis of irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer. Advances in the treatment of disturbances in bile acids absorption and synthesis are also presented. A better understanding of molecular mechanisms regulating bile acid action may have implication for colorectal cancer prevention.

References

  • 1. Alemi F., Poole D.P., Chiu J., Schoonjans K., Cattaruzza F., GriderJ.R., Bunnett N.W., Corvera C.U.: The receptor TGR5 mediates theprokinetic actions of intestinal bile acids and is required for normaldefecation in mice. Gastroenterology, 2013; 144: 145-154
    Google Scholar
  • 2. Appleby R.N., Walters J.R.: The role of bile acids in functional GIdisorders. Neurogastroenterol. Motil., 2014; 26: 1057-1069
    Google Scholar
  • 3. Aziz I., Mumtaz S., Bholah H., Chowdhury F.U., Sanders D.S., FordA.C.: High prevalence of idiopathic bile acid diarrhea among patientswith diarrhea-predominant irritable bowel syndrome basedon Rome III criteria. Clin. Gastroenterol. Hepatol., 2015; 13: 1650-1655
    Google Scholar
  • 4. Bajor A., Törnblom H., Rudling M., Ung K.A., Simrén M.: Increasedcolonic bile acid exposure: a relevant factor for symptoms and treatmentin IBS. Gut, 2015; 64: 84-92
    Google Scholar
  • 5. Ballatori N., Christian W.V., Lee J.Y., Dawson P.A., Soroka C.J., BoyerJ.L., Madejczyk M.S., Li N.: OSTα-OSTβ: a major basolateral bile acidand steroid transporter in human intestinal, renal, and biliary epithelia.Hepatology, 2005; 42: 1270-1279
    Google Scholar
  • 6. Bernstein C., Holubec H., Bhattacharyya A.K., Nguyen H., PayneC.M., Zaitlin B., Bernstein H.: Carcinogenicity of deoxycholate, a secondarybile acid. Arch. Toxicol., 2011; 85: 863-871
    Google Scholar
  • 7. Bernstein H., Bernstein C., Payne C.M., Dvorakova K., Garewal H.:Bile acids as carcinogens in human gastrointestinal cancers. Mutat.Res., 2005; 589: 47-65
    Google Scholar
  • 8. Beuers U., Spengler U., Kruis W., Aydemir U., Wiebecke B., HeldweinW., Weinzierl M., Pape G.R., Sauerbruch T., Paumgartner G.: Ursodeoxycholicacid for treatment of primary sclerosing cholangitis:a placebo-controlled trial. Hepatology, 1992; 16: 707-714
    Google Scholar
  • 9. Biasco G., Paganelli G.M., Brandi G., Brillanti S., Lami F., CallegariC., Gizzi G.: Effect of Lactobacillus acidophilus and Bifidobacteriumbifidum on rectal cell kinetics and fecal pH. Ital. J. Gastroenterol.,1991; 23: 142
    Google Scholar
  • 10. Camilleri M.: Bile acid diarrhea: prevalence, pathogenesis, and therapy. Gut Liver, 2015; 9: 332-339
    Google Scholar
  • 11. Camilleri M.: Advances in understanding of bile acid diarrhea.Expert. Rev. Gastroenterol. Hepatol., 2014; 8: 49-61
    Google Scholar
  • 12. Camilleri M., Busciglio I., Acosta A., Shin A., Carlson P., Burton D.,Ryks M., Rhoten D., Lamsam J., Lueke A., Donato L.J., Zinsmeister A.R.:Effect of increased bile acid synthesis or fecal excretion in irritablebowel syndrome-diarrhea. Am. J. Gastroenterol., 2014; 109: 1621-1630
    Google Scholar
  • 13. Camilleri M., Katzka D.A.: Irritable bowel syndrome: methods,mechanisms, and pathophysiology. Genetic epidemiology and pharmacogeneticsin irritable bowel syndrome. Am. J. Physiol. Gastrointest.Liver Physiol., 2012; 302: G1075-G1084
    Google Scholar
  • 14. Camilleri M., Nadeau A., Tremaine W.J., Lamsam J., Burton D.,Odunsi S., Sweetser S., Singh R.: Measurement of serum 7α-hydroxy-4-cholesten-3-one (or 7αC4), a surrogate test for bile acid malabsorptionin health, ileal disease and irritable bowel syndrome using liquidchromatography-tandem mass spectrometry. Neurogastroenterol.Motil., 2009; 21: 734-743
    Google Scholar
  • 15. Chapman R., Fevery J., Kalloo A., Nagorney D.M., Boberg K.M.,Shneider B., Gores G.J., American Association for the Study of LiverDiseases: Diagnosis and management of primary sclerosing cholangitis.Hepatology, 2010; 51: 660-678
    Google Scholar
  • 16. Chen F., Ma L., Sartor R.B., Li F., Xiong H., Sun A.Q., Shneider B.:Inflammatory-mediated repression of the rat ileal sodium-dependentbile acid transporter by c-fos nuclear translocation. Gastroenterology,2002; 123: 2005-2016
    Google Scholar
  • 17. Choung R.S., Locke G.R.3rd: Epidemiology of IBS. Gastroenterol.Clin. North Am., 2011; 40: 1-10
    Google Scholar
  • 18. Corazza G.R., Ciccarelli R., Caciagli F., Gasbarrini G.: Cyclic AMPand cyclic GMP levels in human colonic mucosa before and duringchenodeoxycholic acid therapy. Gut, 1979; 20: 489-492
    Google Scholar
  • 19. Dawson P.A., Lan T., Rao A.: Bile acid transporters. J. Lipid Res.,2009; 50: 2340-2357
    Google Scholar
  • 20. De Gottardi A., Touri F., Maurer C.A., Perez A., Maurhofer O.,Ventre G., Bentzen C.L., Niesor E.J., Dufour J.F.: The bile acid nuclearreceptor FXR and the bile acid binding protein IBABP are differentlyexpressed in colon cancer. Dig. Dis. Sci., 2004; 49: 982-989
    Google Scholar
  • 21. Debruyne P.R., Bruyneel E.A., Li X., Zimber A., Gespach C., MareelM.M.: The role of bile acids in carcinogenesis. Mutat. Res., 2001;480-481: 359-369
    Google Scholar
  • 22. Ding L., Yang L., Wang Z., Huang W.: Bile acid nuclear receptorFXR and digestive system diseases. Acta. Pharm. Sin. B., 2015;5: 135-144
    Google Scholar
  • 23. Dior M., Delagrèverie H., Duboc H., Jouet P., Coffin B., Brot L.,Humbert L., Trugnan G., Seksik P., Sokol H., Rainteau D., Sabate J.M.:Interplay between bile acid metabolism and microbiota in irritablebowel syndrome. Neurogastroenterol. Motil., 2016; 28: 1330-1340
    Google Scholar
  • 24. Duboc H., Rainteau D., Rajca S., Humbert L., Farabos D., MaubertM., Grondin V., Jouet P., Bouhassira D., Seksik P., Sokol H., CoffinB., Sabaté J.M.: Increase in fecal primary bile acids and dysbiosisin patients with diarrhea-predominant irritable bowel syndrome.Neurogastroenterol. Motil., 2012; 24: 513-520
    Google Scholar
  • 25. European Association for the Study of the Liver: EASL ClinicalPractice Guidelines: management of cholestatic liver diseases. J.Hepatol., 2009; 51: 237-267
    Google Scholar
  • 26. Ferguson J., Walker K., Thomson A.B.: Limitations in the use of14C-glycocholate breath and stool bile acid determinations in patientswith chronic diarrhea. J. Clin. Gastroenterol., 1986; 8: 258-262
    Google Scholar
  • 27. Ferrebee C.B., Dawson P.A.: Metabolic effects of intestinal absorptionand enterohepatic cycling of bile acids. Acta. Pharm. Sin.B., 2015; 5: 129-134
    Google Scholar
  • 28. Glas J., Seiderer J., Fischer D., Tengler B., Pfennig S., Wetzke M.,Beigel F., Olszak T., Weidinger M., Göke B., Ochsenkühn T., FolwacznyM., Müller-Myhsok B., Diegelmann J., Czamara D. i wsp.: Pregnane Xreceptor (PXR/NR1ǀ2) gene haplotypes modulate susceptibility toinflammatory bowel disease. Inflamm. Bowel Dis., 2011; 17: 1917-1924
    Google Scholar
  • 29. Gnewuch C., Liebisch G., Langmann T., Dieplinger B., MuellerT., Haltmayer M., Dieplinger H., Zahn A., Stremmel W., Rogler G.,Schmitz G.: Serum bile acid profiling reflects enterohepatic detoxificationstate and intestinal barrier function in inflammatory boweldisease. World J. Gastroenterol., 2009; 15: 3134-3141
    Google Scholar
  • 30. Gracie D.J., Kane J.S., Mumtaz S., Scarsbrook A.F., ChowdhuryF.U., Ford A.C.: Prevalence of, and predictors of, bile acid malabsorptionin outpatients with chronic diarrhea. Neurogastroenterol. Motil.,2012; 24: 983-e538
    Google Scholar
  • 31. Habior A.: Pierwotne stwardniające zapalenie dróg żółciowych –rozpoznawanie i leczenie. Gastroenterol. Klin., 2010; 2: 14-23
    Google Scholar
  • 32. Habior A., Hartleb M., Milkiewicz P., Gutkowski K., Cichoż-LachH., Mach T., Ciećko-Michalska I., Ferenc M., Bobiński T., Raszeja–Wyszomirska J., Prystupa A., Zych W., Wunsch E., Wasilewicz M.i pozostali członkowie Sekcji Hepatologicznej PTG-E: RekomendacjeSekcji Hepatologicznej Polskiego Towarzystwa Gastroenterologii dotyczącecholestatycznych chorób wątroby – adaptacja wytycznycheuropejskich. Post. N. Med., 2013; 2: 5-38
    Google Scholar
  • 33. Hebanowska A.: Biosynteza kwasów żółciowych i jej regulacja.Postepy Hig. Med. Dosw., 2010; 64: 544-554
    Google Scholar
  • 34. Hofmann A.F.: The continuing importance of bile acids in liverand intestinal disease. Arch. Intern. Med., 1999; 159: 2647-2658
    Google Scholar
  • 35. Hofmann A.F., Eckmann L.: How bile acids confer gut mucosalprotection against bacteria. Proc. Natl. Acad. Sci. USA, 2006; 103:4333-4334
    Google Scholar
  • 36. Imray C.H., Radley S., Davis A., Barker G., Hendrickse C.W., DonovanI.A., Lawson A.M., Baker P.R., Neoptolemos J.P.: Faecal unconjugatedbile acids in patients with colorectal cancer or polyps. Gut,1992; 33: 1239-1245
    Google Scholar
  • 37. Inagaki T., Choi M., Moschetta A., Peng L., Cummins C.L., McDonald J.G., Luo G., Jones S.A., Goodwin B., Richardson J.A., Gerard R.D.,Repa J.J., Mangelsdorf D.J., Kliewer S.A.: Fibroblast growth factor 15functions as an enterohepatic signal to regulate bile acid homeostasis.Cell Metab., 2005; 2: 217-225
    Google Scholar
  • 38. Jahnel J., Fickert P., Hauer A.C., Högenauer C., Avian A., TraunerM.: Inflammatory bowel disease alters intestinal bile acid transporterexpression. Drug Metab. Dispos., 2014; 42: 1423-1431
    Google Scholar
  • 39. Jones S.A.: Physiology of FGF15/19. Adv. Exp. Med. Biol., 2012;728: 171-182
    Google Scholar
  • 40. Jonker J.W., Liddle C., Downes M.: FXR and PXR: potential therapeutictargets in cholestasis. J. Steroid Biochem. Mol. Biol., 2012;130: 147-158
    Google Scholar
  • 41. Jung D., Fantin A.C., Scheurer U., Fried M., Kullak-Ublick G.A.:Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivatedby the glucocorticoid receptor. Gut, 2004; 53: 78-84
    Google Scholar
  • 42. Lidbeck A., Geltner-Allinger U., Orrhage K.M., Ottova L., BrismarB., Gustatsson J.A., Ratter J.J., Nord C.E.: Impact of Lactobacillusacidophilus supplements on the faecal microflora and soluble faecalbile acids in colon cancer patients. Microb. Ecol. Health Dis.,1991; 4: 81-88
    Google Scholar
  • 43. Lindor K.D., Kowdley K.V., Luketic V.A., Harrison M.E., McCashlandT., Befeler A.S., Harnois D., Jorgensen R., Petz J., Keach J.,Mooney J., Sargeant C., Braaten J., Bernard T., King D. i wsp.: Highdoseursodeoxycholic acid for the treatment of primary sclerosingcholangitis. Hepatology, 2009; 50: 808-814
    Google Scholar
  • 44. Lindström L., Boberg K.M., Wikman O., Friis-Liby I., HultcrantzR., Prytz H., Sandberg-Gertzén H., Sangfelt P., Rydning A., Folvik G.,Gangsøy-Kristiansen M., Danielsson A., Bergquist A.: High dose ursodeoxycholicacid in primary sclerosing cholangitis does not preventcolorectal neoplasia. Aliment. Pharmacol. Ther., 2012; 35: 451-457
    Google Scholar
  • 45. Makishima M., Okamoto A.Y., Repa J.J., Tu H., Learned R.M., LukA., Hull M.V., Lustig K.D., Mangelsdorf D.J., Shan B.: Identificationof a nuclear receptor for bile acids. Science, 1999; 284: 1362-1365
    Google Scholar
  • 46. McGarr S.E., Ridlon J.M., Hylemon P.B.: Diet, anaerobic bacterialmetabolism, and colon cancer: a review of the literature. J. Clin.Gastroenterol., 2005; 39: 98-109
    Google Scholar
  • 47. Nguyen A., Bouscarel B.: Bile acids and signal transduction: rolein glucose homeostasis. Cell Signal, 2008; 20: 2180-2197
    Google Scholar
  • 48. Norlin M., Wikvall K.: Enzymes in the conversion of cholesterolinto bile acids. Curr. Mol. Med., 2007; 7: 199-218
    Google Scholar
  • 49. Nowicki M.J., Shneider B.L., Paul J.M., Heubi J.E.: Glucocorticoidsupregulate taurocholate transport by ileal brush-border membrane.Am. J. Physiol., 1997; 273: G197-G203
    Google Scholar
  • 50. Pattni S., Walters J.R.: Recent advances in the understanding ofbile acid malabsorption. Br. Med. Bull., 2009; 92: 79-93
    Google Scholar
  • 51. Pavlidis P., Powell N., Vincent R.P., Ehrlich D., Bjarnason I., HayeeB.: Systematic review: bile acids and intestinal inflammation – luminalaggressors or regulators of mucosal defence? Aliment. Pharmacol.Ther., 2015; 42: 802-817
    Google Scholar
  • 52. Pellicciari R., Costantino G., Fiorucci S.: Farnesoid X receptor:from structure to potential clinical applications. J. Med. Chem., 2005;48: 5383-5403
    Google Scholar
  • 53. Pikuleva I.A.: Cytochrome P450s and cholesterol homeostasis.Pharmacol. Ther., 2006; 112: 761-773
    Google Scholar
  • 54. Ridlon J.M., Alves J.M., Hylemon P.B., Bajaj J.S.: Cirrhosis, bileacids and gut microbiota: unraveling a complex relationship. GutMicrobes, 2013; 4: 382-387
    Google Scholar
  • 55. Ridlon J.M., Kang D.J., Hylemon P.B., Bajaj J.S.: Bile acids andthe gut microbiome. Curr. Opin. Gastroenterol., 2014: 30: 332-338
    Google Scholar
  • 56. Ringel Y., Ringel-Kulka T.: The intestinal microbiota and irritablebowel syndrome. J. Clin. Gastroenterol., 2015; 49: S56-S59
    Google Scholar
  • 57. Russell D.W.: The enzymes, regulation, and genetics of bile acidsynthesis. Annu. Rev. Biochem., 2003; 72: 137-174
    Google Scholar
  • 58. Sayin S.I., Wahlström A., Felin J., Jäntti S., Marschall H.U., BambergK., Angelin B., Hyötyläinen T., Orešič M., Bäckhed F.: Gut microbiotaregulates bile acid metabolism by reducing the levels oftauro-beta-muricholic acid, a naturally occurring FXR antagonist.Cell Metab., 2013; 17: 225-235
    Google Scholar
  • 59. Scaldaferri F., Pizzoferrato M., Ponziani F.R., Gasbarrini G., GasbarriniA.: Use and indications of colestyramine and bile acid sequestrants.Intern. Emerg. Med., 2013; 8: 205-210
    Google Scholar
  • 60. Scarpello J.H., Hodgson E., Howlett H.C.: Effect of metformin onbile salt circulation and intestinal motility in type 2 diabetes mellitus.Diabet. Med., 1998; 15: 651-656
    Google Scholar
  • 61. Shin A., Camilleri M., Vijayvargiya P., Busciglio I., Burton D.,Ryks M., Rhoten D., Lueke A., Saenger A., Girtman A., ZinsmeisterA.R.: Bowel functions, fecal unconjugated primary and secondarybile acids, and colonic transit in patients with irritable bowel syndrome.Clin. Gastroenterol. Hepatol., 2013; 11: 1270-1275
    Google Scholar
  • 62. Smith M.J., Cherian P., Raju G.S., Dawson B.F., Mahon S., BardhanK.D.: Bile acid malabsorption in persistent diarrhoea. J. R. Coll.Physicians Lond., 2000; 34: 448-451
    Google Scholar
  • 63. Stamp D.H.: Three hypotheses linking bile to carcinogenesisin the gastrointestinal tract: certain bile salts have properties thatmay be used to complement chemotherapy. Med. Hypotheses, 2002;59: 398-405
    Google Scholar
  • 64. Stotzer P.O., Abrahamsson H., Bajor A., Sadik R.: Effect of cholestyramineon gastrointestinal transit in patients with idiopathicbile acid diarrhea: a prospective, open-label study. Neuroenterology,2013; 2: 235657
    Google Scholar
  • 65. Vijayvargiya P., Camilleri M., Shin A., Saenger A.: Methods fordiagnosis of bile acid malabsorption in clinical practice. Clin. Gastroenterol.Hepatol., 2013; 11: 1232-1239
    Google Scholar
  • 66. Vitek L.: Bile acid malabsorption in inflammatory bowel disease.Inflamm. Bowel Dis., 2015; 21: 476-483
    Google Scholar
  • 67. Walters J.R.: Bile acid diarrhoea and FGF19: new views on diagnosis,pathogenesis and therapy. Nat. Rev. Gastroenterol. Hepatol.,2014; 11: 426-434
    Google Scholar
  • 68. Walters J.R., Tasleem A.M., Omer O.S., Brydon W.G., Dew T., leRoux C.W.: A new mechanism for bile acid diarrhea: defective feedbackinhibition of bile acid biosynthesis. Clin. Gastroenterol. Hepatol.,2009; 7: 1189-1194
    Google Scholar
  • 69. Wasilewska E., Złotkowska D., Pijagin M.E.: Rola mikroflory jelitoweji bakterii probiotycznych w profilaktyce i rozwoju raka jelitagrubego. Postepy Hig. Med. Dosw., 2013; 67: 837-847
    Google Scholar
  • 70. Wedlake L., A’Hern R., Russell D., Thomas K., Walters J.R., AndreyevH.J.: Systematic review: the prevalence of idiopathic bileacid malabsorption as diagnosed by SeHCAT scanning in patientswith diarrhoea-predominant irritable bowel syndrome. Aliment.Pharmacol. Ther., 2009; 30: 707-717
    Google Scholar
  • 71. Weingardern A.R., Dosa P.I., DeWinter E., Steer C.J., ShaughnessyM.K., Johnson J.R., Khoruts A., Sadowsky M.J.: Changes in colonicbile acid composition following fecal microbiota transplantation aresufficient to control Clostridium difficile germination and growth.PLoS One, 2016; 11: e0147210
    Google Scholar
  • 72. Wilcox C., Turner J., Green J.: Systematic review: the managementof chronic diarrhea due to bile acid malabsorption. Aliment.Pharmacol. Ther., 2014; 39: 923-939
    Google Scholar
  • 73. Winston J.A., Theriot C.M.: Impact of microbial derived secondarybile acids on colonization resistance against Clostridium difficilein the gastrointestinal tract. Anaerobe, 2016; 41: 44-50
    Google Scholar
  • 74. Wong B.S., Camilleri M., Carlson P.J., Guicciardi M.E., Burton D.,McKinzie S., Rao A.S., Zinsmeister A.R., Gores G.J.: A Klothoβ variantmediates protein stability and associates with colon transit inirritable bowel syndrome with diarrhea. Gastroenterology, 2011;140: 1934-1942
    Google Scholar
  • 75. Zhang Z.H., Nolan J.D., Kennie S.L., Johnston I.M., Dew T., DixonP.H., Williamson C., Walters J.R.: Potent stimulation of fibroblastgrowth factor 19 expression in the human ileum by bile acids. Am.J. Physiol. Gastrointest. Liver Physiol., 2013; 304: 940-948
    Google Scholar
  • 76. Zhao Y., Wu J., Li J.V., Zhou N.Y., Tang H., Wang Y.: Gut microbiotacomposition modifies fecal metabolic profiles in mice. J. ProteomeRes., 2013; 12: 2987-2999
    Google Scholar

Full text

Skip to content