Enterohepatic bacterial infections dysregulate the FGF15-FGFR4 endocrine axis

BMC Microbiology

Research Article

Scott Covey¹  Michael T Chow²  Guillaume Romain³  Alfredo Menendez³  Sarah Tremblay³  B Brett Finlay⁴  L Caetano M Antunes⁵  Ellen T Arena⁶ 

[1] Department of Biochemistry and Molecular Biology, The University of British Columbia, V6T 1Z3, Vancouver, BC, Canada;Department of Microbiology and Immunology, University of British Columbia, V6T 1Z3, Vancouver, BC, Canada;Qu Biologics Inc, 887 Great Northern Way, Suite 138, V5T 4T5, Vancouver, BC, Canada;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, J1E 4K8, Sherbrooke, Québec, Canada;Michael Smith Laboratories, The University of British Columbia, V6T 1Z4, Vancouver, BC, Canada;Department of Biochemistry and Molecular Biology, The University of British Columbia, V6T 1Z3, Vancouver, BC, Canada;Michael Smith Laboratories, The University of British Columbia, V6T 1Z4, Vancouver, BC, Canada;Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rua Leopoldo Bulhões, 1480, 21041-210, Rio de Janeiro, RJ, Brazil;Michael Smith Laboratories, The University of British Columbia, V6T 1Z4, Vancouver, BC, Canada;Unité de Pathogénie Microbienne Moléculaire Institut Pasteur, 28 rue du Dr Roux, F – 75724, Paris Cédex 15, France;

关键词: Endocrine;    Metabolism;    Enterohepatic;    Infection;    FGF15;    FGF19;    FGFR4;    βKlotho;    Salmonella;    Listeria;   

DOI  :  10.1186/1471-2180-13-238

 received in 2013-06-18, accepted in 2013-10-26,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundEnterohepatic 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.ResultsInfection 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.ConclusionsBacterial 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.

【 授权许可】

Unknown   
© Romain et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.