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Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy

Key Points

  • Bile acid diarrhoea (BAD) is a prevalent but poorly understood cause of chronic diarrhoea; bile acid malabsorption occurs in ileal disease, but the primary disorder without malabsorption is more common

  • Diagnostic tests for BAD need to be more widely available or new ones further developed

  • Fibroblast growth factor 19 (FGF19) is a bile acid–farnesoid X receptor (FXR)-dependent hormone produced in the ileum

  • Bile acid overproduction due to impaired feedback inhibition by FGF19 might be the cause of the primary disorder

  • Studies in animal models have provided data that: support a role for FGF19 in BAD; show bile acids affect colonic function; and that FXR promotes increases in FGF19 expression and concentration in the blood

  • Therapeutic strategies to increase FGF19 expression and concentration are a new approach to treat BAD

Abstract

Chronic diarrhoea induced by bile acids is common and the underlying mechanisms are linked to homeostatic regulation of hepatic bile acid synthesis by fibroblast growth factor 19 (FGF19). Increasing evidence, including that from several large case series using SeHCAT (selenium homocholic acid taurine) tests for diagnosis, indicates that bile acid diarrhoea (BAD) accounts for a sizeable proportion of patients who would otherwise be diagnosed with IBS. Studies of other approaches for diagnosis of BAD have shown increased bile acid synthesis, increased faecal levels of primary bile acids, dysbiosis and different urinary volatile organic compounds when compared with healthy controls or with other diseases. The role of the ileal hormone FGF19 in BAD has been strengthened: a prospective clinical study has confirmed low FGF19 levels in BAD, and so a test to measure these levels could be developed for diagnosis. In animal models, FGF19 depletion by antibodies produces severe diarrhoea. Bile acids affect colonic function through farnesoid X receptor (FXR) and TGR5 receptors. As well as these effects in the colon, FXR-dependent stimulation of ileal FGF19 production could be a logical mechanism to provide therapeutic benefit in BAD. Further studies of FGF19 in humans hold promise in providing novel treatments for this cause of chronic diarrhoea.

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Figure 1: The percentage of different bile acids in faeces.
Figure 2: Receiver operating characteristic curve for FGF19 in the prediction of a SeHCAT 7-day retention of <10%.
Figure 3: Discriminant function analysis separates urine headspace volatile organic compounds in patients with bile acid diarrhoea compared with those with ulcerative colitis or healthy controls.
Figure 4: A summary of factors proposed to influence bile acid diarrhoea.

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References

  1. Hofmann, A. F. The syndrome of ileal disease and the broken enterohepatic circulation: cholerheic enteropathy. Gastroenterology 52, 752–757 (1967).

    Article  CAS  PubMed  Google Scholar 

  2. Cosnes, J. et al. Classification of the sequelae of bowel resection for Crohn's disease. Br. J. Surg. 81, 1627–1631 (1994).

    Article  CAS  PubMed  Google Scholar 

  3. Jung, D., Fantin, A. C., Scheurer, U., Fried, M. & Kullak-Ublick, G. A. Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor. Gut 53, 78–84 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hofmann, A. F. & Poley, J. R. Cholestyramine treatment of diarrhea associated with ileal resection. N. Engl. J. Med. 281, 397–402 (1969).

    Article  CAS  PubMed  Google Scholar 

  5. Thaysen, E. H. & Pedersen, L. Idiopathic bile acid catharsis. Gut 17, 965–970 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Thomas, P. D. et al. Guidelines for the investigation of chronic diarrhoea, 2nd edition. Gut 52 (Suppl. 5), v1–v15 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Spiller, R. C. & Thompson, W. G. Bowel disorders. Am. J. Gastroenterol. 105, 775–785 (2010).

    Article  PubMed  Google Scholar 

  8. Fromm, H. & Malavolti, M. Bile acid-induced diarrhoea. Clin. Gastroenterol. 15, 567–582 (1986).

    CAS  PubMed  Google Scholar 

  9. van Tilburg, A. J., de Rooij, F. W., van den Berg, J. W. & 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 32, 500–503 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. van Tilburg, A. J., de Rooij, F. W., van den Berg, J. W. & van Blankenstein, M. Primary bile acid malabsorption: a pathophysiologic and clinical entity? Scand. J. Gastroenterol. Suppl. 194, 66–70 (1992).

    Article  CAS  PubMed  Google Scholar 

  11. Bajor, A. et al. Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption. Eur. J. Gastroenterol. Hepatol. 18, 397–403 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Holt, J. A. et al. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 17, 1581–1591 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Inagaki, T. et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell. Metab. 2, 217–225 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Walters, J. R. F. et al. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin. Gastroenterol. Hepatol. 7, 1189–1194 (2009).

    Article  CAS  PubMed  Google Scholar 

  15. Hofmann, A. F. Chronic diarrhea caused by idiopathic bile acid malabsorption: an explanation at last. Expert Rev. Gastroenterol. Hepatol. 3, 461–464 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Walters, J. R. Defining primary bile acid diarrhea: making the diagnosis and recognizing the disorder. Expert Rev. Gastroenterol. Hepatol. 4, 561–567 (2010).

    Article  PubMed  Google Scholar 

  17. Gracie, D. J. et al. Prevalence of, and predictors of, bile acid malabsorption in outpatients with chronic diarrhea. Neurogastroenterol. Motil. 24, 983–e538 (2012).

    Article  CAS  PubMed  Google Scholar 

  18. Khalid, U., Lalji, A., Stafferton, R. & Andreyev, J. Bile acid malabsorption: a forgotten diagnosis? Clin. Medicine 10, 124–126 (2010).

    Article  Google Scholar 

  19. Waters, J. For 40 years, doctors said I had IBS. In fact it was a hormone problem cured by a simple pill. Daily Mail (1 Jan 2013).

  20. Vijayvargiya, P., Camilleri, M., Shin, A. & Saenger, A. Methods for diagnosis of bile acid malabsorption in clinical practice. Clin. Gastroenterol. Hepatol. 11, 1232–1239 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Thaysen, E. H., Orholm, M., Arnfred, T., Carl, J. & Rodbro, P. Assessment of ileal function by abdominal counting of the retention of a γ emitting bile acid analogue. Gut 23, 862–865 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Boyd, G. S., Merrick, M. V., Monks, R. & Thomas, I. L. Se-75-labeled bile acid analogs, new radiopharmaceuticals for investigating the enterohepatic circulation. J. Nucl. Med. 22, 720–725 (1981).

    CAS  PubMed  Google Scholar 

  23. Merrick, M. V., Eastwood, M. A. & Ford, M. J. Is bile acid malabsorption underdiagnosed? An evaluation of accuracy of diagnosis by measurement of SeHCAT retention. Br. Med. J. (Clin. Res. Ed.) 290, 665–668 (1985).

    Article  CAS  Google Scholar 

  24. Sciarretta, G. et al. 75SeHCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit. Gut 28, 970–975 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hofmann, A. F. Enterohepatic circulation of bile acids. Compr. Physiol. 567–596 (2011).

  26. Walters, J. R. F. & Pattni, S. S. Managing bile acid diarrhoea. Ther. Adv. Gastroenterol. 3, 349–357 (2010).

    Article  Google Scholar 

  27. Peters, A. M. & Walters, J. R. Recycling rate of bile acids in the enterohepatic recirculation as a major determinant of whole body 75SeHCAT retention. Eur. J. Nucl. Med. Mol. Imaging 40, 1618–1621 (2013).

    Article  PubMed  Google Scholar 

  28. Nyhlin, H., Merrick, M. V. & Eastwood, M. A. Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT. Gut 35, 90–93 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Smith, M. J. et al. Bile acid malabsorption in persistent diarrhoea. J. R. Coll. Physicians Lond. 34, 448–451 (2000).

    CAS  PubMed  Google Scholar 

  30. Wedlake, L., A'Hern, R., Thomas, K., Walters, J. R. F. & Andreyev, H. J. N. 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. 30, 707–717 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. Borghede, M. K. et al. 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. 22, e137–e140 (2011).

    Article  CAS  PubMed  Google Scholar 

  32. Kurien, M. et al. Bile acid malabsorption: an under-investigated differential diagnosis in patients presenting with diarrhea predominant irritable bowel syndrome type symptoms. Scand. J. Gastroenterol. 46, 818–822 (2011).

    Article  PubMed  Google Scholar 

  33. Pattni, S. S. et al. Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention. Aliment. Pharmacol. Ther. 38, 967–976 (2013).

    Article  CAS  PubMed  Google Scholar 

  34. Smith, M. J. & Perkins, A. C. A survey of the clinical use of SeHCAT in the UK. Nucl. Med. Commun. 34, 306–313 (2013).

    Article  CAS  PubMed  Google Scholar 

  35. NICE. National Institute for Health and Care Excellence [online]. SeHCAT (Tauroselcholic [75Selenium] acid) for the investigation of bile acid malabsorption (BAM) and measurement of bile acid pool loss. http://guidance.nice.org.uk/DT/8 (2013).

  36. Eusufzai, S. Bile acid malabsorption in patients with chronic diarrhoea. Scand. J. Gastroenterol. 28, 865–868 (1993).

    Article  CAS  PubMed  Google Scholar 

  37. Brydon, W. G., Nyhlin, H., Eastwood, M. A. & Merrick, M. V. Serum 7 α-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention in the assessment of bile acid induced diarrhoea. Eur. J. Gastroenterol. Hepatol. 8, 117–123 (1996).

    Article  CAS  PubMed  Google Scholar 

  38. Sauter, G. H., Munzing, W., von, R. C. & 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. 44, 14–19 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Brydon, W. G. et al. An evaluation of the use of serum 7-α-hydroxycholestenone as a diagnostic test of bile acid malabsorption causing watery diarrhea. Can. J. Gastroenterol. 25, 319–323 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  40. 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. 260, 530–536 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Galman, C., Angelin, B. & Rudling, M. Pronounced variation in bile acid synthesis in humans is related to gender, hypertriglyceridaemia and circulating levels of fibroblast growth factor 19. J. Intern. Med. 270, 580–588 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Camilleri, M. et al. Measurement of serum 7α-hydroxy-4-cholesten-3-one (or 7αC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry. Neurogastroenterol. Motil. 21, 734–e43 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wong, B. S. et al. Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin. Gastroenterol. Hepatol. 10, 1009–1015 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Porter, J. L. et al. Accurate enzymatic measurement of fecal bile acids in patients with malabsorption. J. Lab. Clin. Med. 141, 411–418 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Duboc, H. et al. Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol. Motil. 24, 513–517 (2012).

    Article  CAS  PubMed  Google Scholar 

  46. Shin, A. et al. Bowel functions, fecal unconjugated primary and secondary bile acids, and colonic transit in patients with irritable bowel syndrome. Clin. Gastroenterol. Hepatol. 11, 1270–1275 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mekjian, H. S., Phillips, S. F. & Hofmann, A. F. Colonic secretion of water and electrolytes induced by bile acids: perfusion studies in man. J. Clin. Invest. 50, 1569–1577 (1971).

    Article  CAS  PubMed  Google Scholar 

  48. Binder, H. J. & Rawlins, C. L. Effect of conjugated dihydroxy bile salts on electrolyte transport in rat colon. J. Clin. Invest. 52, 1460–1466 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Keely, S. J. et al. Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: Structure–activity relationships. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G290–G297 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Covington, J. A. et al. Application of a novel tool for diagnosing bile acid diarrhoea. Sensors (Basel) 13, 11899–11912 (2013).

    Article  CAS  Google Scholar 

  51. Makishima, M. et al. Identification of a nuclear receptor for bile acids. Science 284, 1362–1365 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Parks, D. J. et al. Bile acids: natural ligands for an orphan receptor. Science 284, 1365–1368 (1999).

    Article  CAS  PubMed  Google Scholar 

  53. Wang, H., Chen, J., Hollister, K., Sowers, L. C. & Forman, B. M. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol. Cell 3, 543–553 (1999).

    Article  CAS  PubMed  Google Scholar 

  54. Jones, S. A. Physiology of FGF15/19. Adv. Exp. Med. Biol. 728, 171–182 (2012).

    Article  CAS  PubMed  Google Scholar 

  55. Oelkers, P., Kirby, L. C., Heubi, J. E. & Dawson, P. A. Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). J. Clin. Invest. 99, 1880–1887 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Montagnani, M., Love, M. W., Rössel, P., Dawson, P. A. & Qvist, P. Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption. Scand. J. Gastroenterol. 36, 1077–1080 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Pattni, S. S., Brydon, W. G., Dew, T. & Walters, J. R. F. Fibroblast growth factor 19 and 7α-hydroxy-4-cholesten-3-one in the diagnosis of patients with possible bile acid diarrhea. Clin. Trans. Gastroenterol. 3, e18 (2012).

    Article  CAS  Google Scholar 

  58. Yu, C. et al. Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J. Biol. Chem. 275, 15482–15489 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. Ito, S. et al. Impaired negative feedback suppression of bile acid synthesis in mice lacking βKlotho. J. Clin. Invest. 115, 2202–2208 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Jung, D. et al. FXR agonists and FGF15 reduce fecal bile acid excretion in a mouse model of bile acid malabsorption. J. Lipid Res. 48, 2693–2700 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Pai, R. et al. Antibody-mediated inhibition of fibroblast growth factor-19 results in increased bile acids synthesis and ileal malabsorption of bile acids in cynomolgus monkeys. Toxicol. Sci. 126, 446–456 (2012).

    Article  CAS  PubMed  Google Scholar 

  62. Yu, X. X. et al. Peripheral reduction of FGFR4 with antisense oligonucleotides increases metabolic rate and lowers adiposity in diet-induced obese mice. PLoS ONE 8, e66923 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Wong, B. S. et al. A Klotho-β variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea. Gastroenterology 140, 1934–1942 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Rao, A. S. et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology 139, 1549–1558 (2010).

    Article  CAS  PubMed  Google Scholar 

  65. Wong, B. S. et al. Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea. Dig. Dis. Sci. 57, 1222–1226 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Gadaleta, R. M. et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut 60, 463–472 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Lenicek, M. et al. Bile acid malabsorption in inflammatory bowel disease: assessment by serum markers. Inflamm. Bowel. Dis. 17, 1322–1327 (2010).

    Article  PubMed  Google Scholar 

  68. Nolan, J. D., Johnston, I. M. & Walters, J. R. Altered enterohepatic circulation of bile acids in Crohn's disease and their clinical significance: a new perspective. Expert Rev. Gastroenterol. Hepatol. 7, 49–56 (2013).

    Article  CAS  PubMed  Google Scholar 

  69. Vergnes, L., Lee, J. M., Chin, R. G., Auwerx, J. & Reue, K. Diet1 functions in the FGF15/19 enterohepatic signaling axis to modulate bile acid and lipid levels. Cell Metab. 17, 916–928 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kir, S. et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science 331, 1621–1624 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Stejskal, D., Karpisek, M., Hanulova, Z. & Stejskal, P. Fibroblast growth factor-19: development, analytical characterization and clinical evaluation of a new ELISA test. Scand. J. Clin. Lab. Invest. 68, 501–507 (2008).

    Article  CAS  PubMed  Google Scholar 

  72. Pournaras, D. J. et al. The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology 153, 3613–3619 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 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. 99, 711–718 (2004).

    Article  PubMed  Google Scholar 

  74. Fu, T. et al. Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19 by targeting a membrane coreceptor β-Klotho. Proc. Natl Acad. Sci. USA 109, 16137–16142 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Miyata, M. et al. Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19. J. Steroid Biochem. Mol. Biol. 132, 41–47 (2012).

    Article  CAS  PubMed  Google Scholar 

  76. Schmidt, D. R. et al. Regulation of bile acid synthesis by fat-soluble vitamins A and D. J. Biol. Chem. 285, 14486–14494 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zhang, J. H. et al. Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids. Am. J. Physiol. Gastrointest. Liver Physiol. 304, G940–G948 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Pellicciari, R. et al. 6α-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J. Med. Chem. 45, 3569–3572 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Mroz, M. S. et al. Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo. Gut http://dx.doi.org/10.1136/gutjnl-2013-305088.

  80. Kawamata, Y. et al. A G protein-coupled receptor responsive to bile acids. J. Biol. Chem. 278, 9435–9440 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Maruyama, T. et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochem. Biophys. Res. Commun. 298, 714–719 (2002).

    Article  CAS  PubMed  Google Scholar 

  82. Alemi, F. et al. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology 144, 145–154 (2013).

    Article  CAS  PubMed  Google Scholar 

  83. Pellicciari, R. et al. Discovery of 6α-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity. J. Med. Chem. 52, 7958–7961 (2009).

    Article  CAS  PubMed  Google Scholar 

  84. Ward, J. B., Mroz, M. S. & Keely, S. J. The bile acid receptor, TGR5, regulates basal and cholinergic-induced secretory responses in rat colon. Neurogastroenterol. Motil. 25, 708–711 (2013).

    Article  CAS  PubMed  Google Scholar 

  85. Iguchi, Y. et al. Effects of chemical modification of ursodeoxycholic acid on TGR5 activation. Biol. Pharm. Bull. 34, 1–7 (2011).

    Article  CAS  PubMed  Google Scholar 

  86. Camilleri, M. et al. Association of bile acid receptor TGR5 variation and transit in health and lower functional gastrointestinal disorders. Neurogastroenterol. Motil. 23, 995–999 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sayin, S. I. et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-β-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17, 225–235 (2013).

    Article  CAS  PubMed  Google Scholar 

  88. US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  89. Mudaliar, S. et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 145, 574–582 (2013).

    Article  CAS  PubMed  Google Scholar 

  90. Johnston, I. M., Nolan, J. D., Dew, T., Shapiro, D. & Walters, J. R. F. 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, S60 (2013).

    Article  Google Scholar 

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Research support from the Bardhan Research and Education Trust and the Broad Foundation is gratefully acknowledged.

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J.R.F.W. has been a member of advisory committees or review panels and has received fees for consulting, speaking or teaching from Albireo AB, GE Healthcare, GLG Research, Intercept Pharmaceuticals, Novartis, NGM Biopharmaceuticals, Pendopharm and Sanofi.

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Walters, J. Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol 11, 426–434 (2014). https://doi.org/10.1038/nrgastro.2014.32

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