Administration of defined microbiota is protective in a murine Salmonella infection model.
Author(s)
Type
Journal Article
Abstract
Salmonella typhimurium is a major cause of diarrhea and causes significant morbidity and mortality worldwide, and perturbations of the gut microbiota are known to increase susceptibility to enteric infections. The purpose of this study was to investigate whether a Microbial Ecosystem Therapeutic (MET-1) consisting of 33 bacterial strains, isolated from human stool and previously used to cure patients with recurrent Clostridium difficile infection, could also protect against S. typhimurium disease. C57BL/6 mice were pretreated with streptomycin prior to receiving MET-1 or control, then gavaged with S. typhimurium. Weight loss, serum cytokine levels, and S. typhimurium splenic translocation were measured. NF-κB nuclear staining, neutrophil accumulation, and localization of tight junction proteins (claudin-1, ZO-1) were visualized by immunofluorescence. Infected mice receiving MET-1 lost less weight, had reduced serum cytokines, reduced NF-κB nuclear staining, and decreased neutrophil infiltration in the cecum. MET-1 also preserved cecum tight junction protein expression, and reduced S. typhimurium translocation to the spleen. Notably, MET-1 did not decrease CFUs of Salmonella in the intestine. MET-1 may attenuate systemic infection by preserving tight junctions, thereby inhibiting S. typhimurium from gaining access to the systemic circulation. We conclude that MET-1 may be protective against enteric infections besides C. difficile infection.
Date Issued
2015-11-04
Date Acceptance
2015-09-28
Citation
Scientific Reports, 2015, 5
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
5
Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0 International License. The
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Creative Commons license, users will need to obtain permission from the license holder to reproduce
the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
images or other third party material in this article are included in the article’s Creative Commons
license, unless indicated otherwise in the credit line; if the material is not included under the
Creative Commons license, users will need to obtain permission from the license holder to reproduce
the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
License URL
Identifier
PII: srep16094
Subjects
Animals
Bacteria
Body Weight
Cecum
Claudin-1
Colitis
Cytokines
Disease Models, Animal
Feces
Humans
Intestinal Mucosa
Intestines
Mice
Mice, Inbred C57BL
Microbiota
Mucins
NF-kappa B
Neutrophils
Phylogeny
RNA, Ribosomal, 16S
Salmonella Infections, Animal
Salmonella typhimurium
Sequence Analysis, DNA
Spleen
Tight Junctions
Tumor Necrosis Factor-alpha
Zonula Occludens-1 Protein
Publication Status
Published online
Article Number
16094