Study Title:


Study Abstract

Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell1, 2, 3, 4, 5. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses3. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4+ CD45RBhi T cells in Rag1−/− mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host–microbe interactions establish immunological homeostasis in the gut.

From press release:


Published in the journal Nature today, the Japanese study shows that butyrate, a by-product of the digestion of dietary fiber by gut microbes, acts as an epigenetic switch that boosts the immune system by inducing the production of regulatory T cells in the gut.

Previous studies have shown that patients suffering from inflammatory bowel disease lack butyrate-producing bacteria and have lower levels of butyrate in their gut. However, butyrate's anti-inflammatory properties were attributed to its role as main energy source for the cells lining the colon. This study is the first to provide a molecular basis for the role of butyrate on the production of regulatory T lymphocytes.






Study Information

Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Takaho A. Endo, Gaku Nakato, et al.
2013 November
University of Tokyo and Keio University

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