Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes
By Eliana Mariño, James L. Richards, Keiran H McLeod, D. Stanley, Y. Yap, Jacinta Knight, Craig I. McKenzie, J. Kranich, A. Oliveira, F. Rossello and 14 more. Nature Immunology, 2017
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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.
Subfields: Genetics, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/7477039bb10b1f44c09d3b82f629ea7fcbaabbc0
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Citations in the corpus
- Short-chain fatty acids: linking diet, the microbiome and immunity (2024, neutral): “Several mechanisms seem to account for the protective effects of butyrate against diabetes, including a reduction in the frequency of autoreactive T cells 195,197 .”
- Microbiota in health and diseases (2022, result): “In addition, T1DM patients may exhibit decreased levels of SCFA butyrate-producing bacteria, which are key factors in decreasing chronic inflammation and maintaining intestinal homeostasis.(169) This finding was reinforced by other case-control studies which showed that the levels of R.”