title: Enterohepatic bacterial infections dysregulate the FGF15-FGFR4 endocrine axis.
abstract: BACKGROUND
  Enterohepatic bacterial infections have the potential to affect multiple physiological processes of the body. Fibroblast growth factor 15/19 (FGF15 in mice, FGF19 in humans) is a hormone that functions as a central regulator of glucose, lipid and bile acid metabolism. FGF15/19 is produced in the intestine and exert its actions on the liver by signaling through the FGFR4-βKlotho receptor complex. Here, we examined the in vivo effects of enterohepatic bacterial infection over the FGF15 endocrine axis.
  
  
  RESULTS
  Infection triggered significant reductions in the intestinal expression of Fgf15 and its hepatic receptor components (Fgfr4 and Klb (βKlotho)). Infection also resulted in alterations of the expression pattern of genes involved in hepatobiliary function, marked reduction in gallbladder bile volumes and accumulation of hepatic cholesterol and triglycerides. The decrease in ileal Fgf15 expression was associated with liver bacterial colonization and hepatobiliary pathophysiology rather than with direct intestinal bacterial pathogenesis.
  
  
  CONCLUSIONS
  Bacterial pathogens of the enterohepatic system can disturb the homeostasis of the FGF15/19-FGFR4 endocrine axis. These results open up a possible link between FGF15/19-FGFR4 disruptions and the metabolic and nutritional disorders observed in infectious diseases.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Romain
authors.forename: Sarah
authors.initials: S
authors.lastname: Tremblay
authors.forename: Ellen T
authors.initials: ET
authors.lastname: Arena
authors.forename: L Caetano M
authors.initials: LC
authors.lastname: Antunes
authors.forename: Scott
authors.initials: S
authors.lastname: Covey
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chow
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.affiliation: Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, University of Sherbrooke, Cancer Research Pavilion, Rm Z8-1072, 3201, rue Jean-Mignault, Sherbrooke, Québec J1E 4K8, Canada. alfredo.menendez@usherbrooke.ca.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Menendez
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000382:microbiology / Q000473:pathology*; D020869:Gene Expression Profiling; D008088:Listeriosis / Q000473:pathology*; D008099:Liver / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000473:pathology*
chemical_list: C108526:fibroblast growth factor 15, mouse; D005346:Fibroblast Growth Factors; C496372:Fgfr4 protein, mouse; D051499:Receptor, Fibroblast Growth Factor, Type 4