Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in VSports app下载. gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure V体育官网. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. .

. 2013 Oct 29:13:238.
doi: 10.1186/1471-2180-13-238.

Enterohepatic bacterial infections dysregulate the FGF15-FGFR4 endocrine axis

Guillaume Romain, Sarah Tremblay, Ellen T Arena, L Caetano M Antunes, Scott Covey, Michael T Chow, B Brett Finlay, Alfredo Menendez  1
Affiliations

Enterohepatic bacterial infections dysregulate the FGF15-FGFR4 endocrine axis

Guillaume Romain et al. BMC Microbiol. .

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 VSports手机版. 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 V体育安卓版. 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. V体育ios版.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Oral infection with Salmonella typhimurium SL1344 decreases the expression of Fgf15 in the ileum. (A) bacterial counts in infected ilea and livers; animals were arbitrarily grouped into low, medium and high infection levels (100-103, 104-105 and >106 cfu/mg, respectively roughly corresponding to 72, 96 and 120 hours post-infection; UI: uninfected). (B) relative levels of Fgf15 transcripts in the ilea of infected mice (data by qPCR). (C) H&E staining of ileum sections from representative uninfected and orally Salmonella-infected animals (ileal colonization of the infected animal = 2.2 × 106 cfu/mg); scale bars are 200 μm. (D) H&E staining of liver sections from representative uninfected and orally Salmonella-infected animals (liver colonization of the infected animal = 1.7 × 105 cfu/mg); scale bars are 800 and 400 μm.
Figure 2
Figure 2
Liver colonization drives the downregulation of ileal Fgf15 expression. (A) relative levels of Fgf15 transcripts in the ileum of mice infected orally or intravenously with Listeria monocytogenes. (B) transcript levels of genes involved in liver biliary metabolism in mice infected intravenously with Listeria monocytogenes, relative to the levels of uninfected animals (defined as 1, dashed line). (C) relative levels of Fgf15 transcripts in the ilea of mice infected intravenously with Salmonella typhimurium SB103 (invA), at 120 hours post-infection. Data by qPCR, *p < 0.05.
Figure 3
Figure 3
Infection with Salmonella decreases the expression of FXR-target genes in the ileum. (A) Relative levels of Fabp6, Nr0b2 and Osta transcripts in the ileum of mice orally infected with Salmonella typhimurium SL1344. Animals were arbitrarily grouped into low, medium and high infection levels (100-103, 104-105 and >106 cfu/mg, respectively roughly corresponding to 72, 96 and 120 hours post-infection; UI: uninfected). (B)Fgf15 transcript levels in the ilea of uninfected mice fed 5% cholestyramine diet. Data by qPCR, **p < 0.01; ***p < 0.001; ****p < 0.0001.
Figure 4
Figure 4
Salmonella infection perturbs the host’s hepatobiliary homeostasis. (A) bile volumes recovered from the gallbladders of mice orally infected with Salmonella at the indicated hours post-infection (hpi). (B) Transcript levels of hepatic genes involved in liver biliary metabolism in mice infected with Salmonella, relative to the levels of uninfected animals (defined as 1, dashed line) at 24, 72 and 120 hours post-infection. Data by qPCR.
Figure 5
Figure 5
Salmonella infection downregulates the neutral bile acid synthesis pathway. (A) relative levels of liver Cyp7a1 transcripts in mice infected with Salmonella. (B) CYP7A1 western blot of liver lysates. (C) Cholesterol and (D) triglycerides accumulation in the liver of Salmonella-infected vs. uninfected mice, (*p < 0.05; ****p < 0.0001).
Figure 6
Figure 6
Salmonella infection causes the loss of the hepatic FGF15 receptor complex. (A) relative levels of Fgfr4 and (B)Klb (βKlotho) transcripts in the livers of mice infected with Salmonella. The animals analyzed in (A) and (B) are from the high-infection group in Figure 1, the data is by qPCR, (**p < 0.01; ***p < 0.001). (C) FGFR4 and βKlotho western blots of liver lysates. (D) FGFR4 and βKlotho immunostaining of uninfected (top panel) and Salmonella-infected (bottom panel) liver samples. The figure shows a single, representative hepatocyte in each case. Scale bar is 5 μm.
See this image and copyright information in PMC

References

    1. Powanda MC, Beisel WR. Metabolic effects of infection on protein and energy status. J Nutr. 2003;133(1):322S–327S. - PubMed
    1. McGuinness OP. Defective glucose homeostasis during infection. Annu Rev Nutr. 2005;25:9–35. doi: 10.1146/annurev.nutr.24.012003.132159. - DOI - PubMed
    1. Khosla SN. Typhoyd fever. Its cause, transmission and prevention. New Delhi: Atlantic Publishers; 2008.
    1. Antunes LC, Arena ET, Menendez A, Han J, Ferreira RB, Buckner MM, Lolic P, Madilao LL, Bohlmann J, Borchers CH. et al.Impact of salmonella infection on host hormone metabolism revealed by metabolomics. Infect Immun. 2011;79(4):1759–1769. doi: 10.1128/IAI.01373-10. - V体育官网 - DOI - PMC - PubMed
    1. Parry CM. In: Salmonella infections: clinical, immunological and molecular aspects. Mastroeni P, Maskell D, editor. Cambridge, New York: Cambridge University Press; 2006. Epidemiological and clinical aspects of human typhoid fever.

Publication types

Substances

LinkOut - more resources (V体育平台登录)