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Nat Immunol. 2017 May;18(5):552-562. doi: 10.1038/ni.3713. Epub 2017 Mar 27.

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

Author information

1
Infection and Immunity Program, Biomedicine Discovery Institute, Department of Biochemistry, Monash University, Clayton, Australia.
2
Central Queensland University, School of Medical and Applied Sciences, Rockhampton, Australia.
3
Institute for Immunology, Ludwig Maximilians University, Munich, Munich, Germany.
4
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
5
Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia.
6
Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Clayton, Australia.
7
Australian Regenerative Medicine Institute, Monash University, Clayton, Australia.
8
Islet Biology Laboratory, St Vincent's Institute, Fitzroy, Australia.
9
Nutritional Immunometabolism Node Laboratory, Charles Perkins Centre, University of Sydney, Sydney, Australia.
10
School of Medical Sciences, University of Sydney, Sydney, Australia.
11
Comparative Genomics Centre, Molecular Sciences, James Cook University, Townsville, Australia.
12
Harry Perkins Institute for Medical Research, Nedlands, Australia.
13
Infection and Immunity Program, Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Australia.
14
School of Science, RMIT University, Bundoora West Campus, Bundoora, Australia.
15
CSIRO Health and Biosecurity, North Ryde, Australia.
16
CSIRO Health and Biosecurity, Adelaide, Australia.
17
Walter &Eliza Hall Institute of Medical Research, Parkville, Australia.

Abstract

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.

PMID:
28346408
DOI:
10.1038/ni.3713
[Indexed for MEDLINE]

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