title: Altered enterohepatic circulation of bile acids in Crohn's disease and their clinical significance: a new perspective.
abstract: The role of bile acids (BA) extends far beyond lipid digestion and cholesterol metabolism. The transcriptional regulation of multiple genes within the liver and intestine are under their influence. BA exert these effects through binding and activating receptors in much the same way as endocrine hormones. The farnesoid X receptor (FXR) is the intracellular transcription factor for BA; TGR5 is the cell-surface receptor. The main target genes of FXR are those involved in BA and cholesterol metabolism. Yet more recently, FXR has also been shown to influence and promote certain protective pathways within the liver. These pathways are being harnessed by semisynthetic BAs in Phase II and III clinical trials. FXR activation within the intestine is also associated with similar protective pathways. This article examines the consequences of altered FXR activation in the context of BA malabsorption in Crohn's disease and the potential benefits of FXR agonists in Crohn's disease.
authors.affiliation: Department of Gastroenterology, Imperial College NHS Trust, Hammersmith Hospital, Section of Hepatology & Gastroenterology, Imperial College, London, W12 0HS, UK.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Nolan
authors.forename: Ian M
authors.initials: IM
authors.lastname: Johnston
authors.forename: Julian R F
authors.initials: JR
authors.lastname: Walters
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000378:metabolism*; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D015195:Drug Design; D004764:Enterohepatic Circulation; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000893:Anti-Inflammatory Agents; D001647:Bile Acids and Salts; D016207:Cytokines; D005346:Fibroblast Growth Factors; D005765:Gastrointestinal Agents; D018836:Inflammation Mediators; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C117476:FGF19 protein, human