The Farnesoid X Receptor: Good for BAD.
Diarrhea is a feature of several chronic intestinal disorders that are associated with increased delivery of bile acids into the colon. Although the prevalence of bile acid diarrhea is high, affecting approximately 1% of the adult population, current therapies often are unsatisfactory. By virtue of its capacity to inhibit colonic epithelial fluid secretion and to down-regulate hepatic bile acid synthesis through induction of the ileal fibroblast growth factor 19 release, the nuclear bile acid receptor, farnesoid X receptor, represents a promising target for the development of new therapeutic approaches. Here, we review our current understanding of the pathophysiology of bile acid diarrhea and the current evidence supporting a role for farnesoid X receptor agonists in treatment of the disease.
Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Stephen J
SJ
Keely
Division of Digestive Diseases, Hammersmith Hospital, Imperial College London, London, United Kingdom.
Julian R F
JR
Walters
ASBT, apical sodium-linked bile acid transporter; BAD, bile acid diarrhea; Bile Acid Diarrhea; C4, 7α-hydroxy-4-cholesten-3-one; CA, cholic acid; CDCA, chenodeoxycholic acid; Chloride Secretion; DCA, deoxycholic acid; EHC, enterohepatic circulation; Enterohepatic Circulation; Epithelium; FGF-19; FGF19, fibroblast growth factor 19; FXR, farnesoid X receptor; LCA, lithocholic acid; OCA, obeticholic acid