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Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes

journal contribution
posted on 20.12.2017, 00:00 by E Mariño, JL Richards, KH McLeod, Dragana Stanley, YA Yap, J Knight, C McKenzie, J Kranich, AC Oliveira, FJ Rossello
Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance. Feeding mice a combined acetate- and butyrate-yielding diet provided complete protection, which suggested that acetate and butyrate might operate through distinct mechanisms. Acetate markedly decreased the frequency of autoreactive T cells in lymphoid tissues, through effects on B cells and their ability to expand populations of autoreactive T cells. A diet containing butyrate boosted the number and function of regulatory T cells, whereas acetate- and butyrate-yielding diets enhanced gut integrity and decreased serum concentration of diabetogenic cytokines such as IL-21. Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell-dependent autoimmune diseases. © 2017 Nature America, Inc.

History

Volume

18

Issue

5

Start Page

552

End Page

562

Number of Pages

11

eISSN

1529-2916

ISSN

1529-2908

Publisher

Nature Publishing Group, USA

Peer Reviewed

Yes

Open Access

No

External Author Affiliations

Monash University; St Vincent’s Institute, Australia; University of Sydney; RMIT; CSIRO; James Cook University; Universidade Federal do Rio de Janeiro; Ludwig Maximilians University, Germany; Harry Perkins Institute for Medical Research, Australia; 17Walter & Eliza Hall Institute of Medical Research, Australia;

Era Eligible

Yes

Journal

Nature Immunology

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