A murine model of diarrhea, growth impairment and metabolic disturbances with Shigella flexneri infection and the role of zinc deficiency
Author(s)
Type
Journal Article
Abstract
Shigella is one of the major enteric pathogens worldwide. We present a murine model of S. flexneri infection and investigate the role of zinc deficiency (ZD). C57BL/6 mice fed either standard chow (HC) or ZD diets were pretreated with an antibiotic cocktail and received S. flexneri strain 2457T orally. Antibiotic pre-treated ZD mice showed higher S. flexneri colonization than non-treated mice. ZD mice showed persistent colonization for at least 50 days post-infection (pi). S. flexneri-infected mice showed significant weight loss, diarrhea and increased levels of fecal MPO and LCN in both HC and ZD fed mice. S. flexneri preferentially colonized the colon, caused epithelial disruption and inflammatory cell infiltrate, and promoted cytokine production which correlated with weight loss and histopathological changes. Infection with S. flexneri ΔmxiG (critical for type 3 secretion system) did not cause weight loss or diarrhea, and had decreased stool shedding duration and tissue burden. Several biochemical changes related to energy, inflammation and gut-microbial metabolism were observed. Zinc supplementation increased weight gains and reduced intestinal inflammation and stool shedding in ZD infected mice. In conclusion, young antibiotic-treated mice provide a new model of oral S. flexneri infection, with ZD promoting prolonged infection outcomes.
Date Issued
2019-02-03
Date Acceptance
2018-12-19
Citation
Gut Microbes, 2019, 10 (5), pp.615-630
ISSN
1949-0984
Publisher
Taylor & Francis
Start Page
615
End Page
630
Journal / Book Title
Gut Microbes
Volume
10
Issue
5
Copyright Statement
© 2019 The Author(s). Published with license by Taylor & Francis Group, LLCThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricteduse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor
Bill & Melinda Gates Foundation
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30712505
Grant Number
Prime Award OPP1066140
Subjects
Shigellosis
intestinal microbiota
mouse model
urine metabolomics
zinc deficiency
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-02-03