Intestinal epithelial stem cells reside at the base of intestinal crypts. In Cell, Kaiko et al. identify the microbial metabolite butyrate as an inhibitor of intestinal stem-cell proliferation. Butyrate is a product of bacterial fermentation of dietary fiber. At concentrations found in the mouse colon (1–5 mM), butyrate suppresses epithelial-cell proliferation in vitro and in the crypt-less zebrafish colon or after injury-induced exposure of stem cells in the mouse colon. This inhibitory effect is reversed by culture with differentiated colon epithelial cells, which metabolize butyrate as an energy source. Mice that lack the enzyme that converts butyrate to acetyl-CoA have less proliferation of colonic epithelial cells. Butyrate inhibits histone-deacetylase activity, induces alterations to gene expression and increases binding of the transcription factor Foxo3 to the promoters of the genes encoding the cell-cycle regulators Cdkn1a, Cdk1c and Gadd45b in intestinal stem cells. In vivo, Foxo inhibitors 'rescue' the effect of butyrate on epithelial-cell proliferation.

Cell (2 June 2016) doi:10.1016/j.cell.2016.05.018