Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer

Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis associated colorectal cancer (CAC). Here we report a role for the NAD+ dependent histone deacetylase SIRT1 in the control of anti bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1int / ) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view the effects on mouse intestinal cell maturation are mediated by SIRT1 dependent changes in the acetylation status of SPDEF a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC. © 2014 Lo Sasso et al.