Enterohepatic bacterial infections dysregulate the FGF15-FGFR4 endocrine axis

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• 作者：Guillaume Romain (8)
  Sarah Tremblay (8)
  Ellen T Arena (12) (9)
  L Caetano M Antunes (13) (9)
  Scott Covey (10)
  Michael T Chow (11) (14)
  B Brett Finlay (10) (9)
  Alfredo Menendez (8)
  
• 关键词：Endocrine ; Metabolism ; Enterohepatic ; Infection ; FGF15 ; FGF19 ; FGFR4 ; βKlotho ; Salmonella ; Listeria
• 刊名：BMC Microbiology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：13
• 期：1
• 全文大小：855 KB
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• 作者单位：Guillaume Romain (8)
  Sarah Tremblay (8)
  Ellen T Arena (12) (9)
  L Caetano M Antunes (13) (9)
  Scott Covey (10)
  Michael T Chow (11) (14)
  B Brett Finlay (10) (9)
  Alfredo Menendez (8)
  
  8. 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
  12. Unité de Pathogénie Microbienne Moléculaire Institut Pasteur, 28 rue du Dr Roux, F -75724, Paris Cédex 15, France
  9. Michael Smith Laboratories, The University of British Columbia, Vancouver, BC, V6T 1Z4, Canada
  13. Escola Nacional de Saúde Pública Sergio Arouca, Funda??o Oswaldo Cruz, Rua Leopoldo Bulh?es, 1480, Rio de Janeiro, RJ, 21041-210, Brazil
  10. Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada
  11. Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada
  14. Qu Biologics Inc, 887 Great Northern Way, Suite 138, Vancouver, BC, V5T 4T5, Canada
  
• ISSN：1471-2180

文摘

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.