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

Nat Rev Gastroenterol Hepatol. 2014 Jul;11(7):426-34. doi: 10.1038/nrgastro.2014.32. Epub 2014 Mar 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / analysis
  • Bile Acids and Salts / physiology*
  • Chronic Disease
  • Diarrhea / diagnosis
  • Diarrhea / etiology*
  • Feces / chemistry
  • Fibroblast Growth Factors / physiology*
  • Humans
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, G-Protein-Coupled / physiology

Substances

  • Bile Acids and Salts
  • FGF19 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • farnesoid X-activated receptor
  • Fibroblast Growth Factors