Enterococcus durans TN-3 Induces Regulatory T Cells and Suppresses the Development of Dextran Sulfate Sodium (DSS)-Induced Experimental Colitis

PLoS One. 2016 Jul 20;11(7):e0159705. doi: 10.1371/journal.pone.0159705. eCollection 2016.

Abstract

Background and aims: Probiotic properties of Enterococcus strains have been reported previously. In this study, we investigated the effects of Enterococcus (E.) durans TN-3 on the development of dextran sulfate sodium (DSS) colitis.

Methods: BALB/c mice were fed with 4.0% DSS in normal chow. Administration of TN-3 (10mg/day) was initiated 7days before the start of DSS feeding. Mucosal cytokine expression was analyzed by real time-PCR and immunohistochemistry. The lymphocyte subpopulation were analyzed by flow cytometry. The gut microbiota profile was analyzed by a terminal-restriction fragment length polymorphism method (T-RFLP).

Results: The disease activity index and histological colitis score were significantly lower in the DSS plus TN-3 group than in the DSS group. The mucosal mRNA expression of proinflammatory cytokines (IL-1β, IL-6, IL-17A and IFN-γ) decreased significantly in the DSS plus TN-3 group as compared to the DSS group. The proportion of regulatory T cells (Treg cells) in the mucosa increased significantly in the DSS plus TN-3 group as compared to the DSS group. Both fecal butyrate levels and the diversity of fecal microbial community were significantly higher in the TN-3 plus DSS group than in the DSS group.

Conclusions: E. durans TN-3 exerted an inhibitory effect on the development of DSS colitis. This action might be mediated by the induction of Treg cells and the restoration of the diversity of the gut microbiota.

MeSH terms

  • Animals
  • Butyrates / chemistry
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / immunology
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Enterococcus / chemistry
  • Enterococcus / metabolism*
  • Feces / chemistry
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Probiotics / administration & dosage*
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Butyrates
  • Cytokines
  • Dextran Sulfate

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, (15K08967, 15K19322), https://www.jsps.go.jp/english/e-grants/, the Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan, 067, http://www.mhlw.go.jp/english/, Smoking Research Foundation, 1828, http://www.srf.or.jp/english/, Nichinichi Pharmaceutical Corporation Ltd provided support in the form of salaries for T.S, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Nichinichi Pharmaceutical Corporation Ltd and T.S. provided E. durans (TN-3) used in this study.