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      Stressor exposure has prolonged effects on colonic microbial community structure in Citrobacter rodentium-challenged mice

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          Abstract

          Stressor exposure significantly affects the colonic mucosa-associated microbiota, and exacerbates Citrobacter rodentium-induced inflammation, effects that can be attenuated with probiotic Lactobacillus reuteri. This study assessed the structure of the colonic mucosa-associated microbiota in mice exposed to a social stressor (called social disruption), as well as non-stressed control mice, during challenge with the colonic pathogen C. rodentium. Mice were exposed to the social stressor or home cage control conditions for six consecutive days and all mice were challenged with C. rodentium immediately following the first exposure to the stressor. In addition, mice received probiotic L. reuteri, or vehicle as a control, via oral gavage following each stressor exposure. The stressor-exposed mice had significant differences in microbial community composition compared to non-stressed control mice. This difference was first evident following the six-cycle exposure to the stressor, on Day 6 post- C. rodentium challenge, and persisted for up to 19 days after stressor termination. Mice exposed to the stressor had different microbial community composition regardless of whether they were treated with L. reuteri or treated with vehicle as a control. These data indicate that stressor exposure affects the colonic microbiota during challenge with C. rodentium, and that these effects are long-lasting and not attenuated by probiotic L. reuteri.

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          Most cited references39

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway

            Background & Aims While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet. Methods C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high–fat (60 kcal % fat) diet (HFD) for 8 weeks. Results HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-κB in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice. Conclusions HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity.
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              How stress influences the immune response.

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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                27 March 2017
                2017
                : 7
                : 45012
                Affiliations
                [1 ]Biosciences, College of Dentistry, The Ohio State University , Columbus, OH, USA
                Author notes
                [*]

                Present address: Department of Molecular Virology and Immunology, Baylor College of Medicine, Houston, TX, USA.

                [†]

                Present address: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA.

                [‡]

                Present address: Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH USA.

                Article
                srep45012
                10.1038/srep45012
                5366811
                b9d80ce6-00fc-4654-b186-242f5f318cea
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The 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/

                History
                : 21 September 2016
                : 20 February 2017
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