Figure 1. The commensal bacteria-butyrate-Treg cell axis of inflammatory regulation in the gut. Certain commensal bacteria abundantly produce butyrate through fermentation of dietary fiber and other substrates. Two recent studies1,2 found that butyrate promotes histone H3 lysine acetylation of the promoter and enhancer elements of forkhead box P3 (Foxp3) in naïve mouse Cd4+ T cells, eventually inducing the differentiation of Treg cells. Treg cells in turn contribute to mucosal health by regulating the inflammatory response in the gut.

Ex vivo, Arpaia et al. showed that greater levels of Foxp3 acetylation and Treg cell differentiation could be achieved by coculturing butyrate-treated dendritic cells with naïve Cd4+ T cells rather than directly treating naïve Cd4+ T cells with butyrate. These results suggest that butyrate works through more than one immune cell population. (Figure based on Supplemental Figure 22 in ref. 1.)