Papers in the Biological Sciences


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Lo Sasso G, Ryu D, Mouchiroud L, Fernando SC, Anderson CL, et al. (2014) Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer. PLoS ONE 9(7): e102495. doi:10.1371/journal.pone.0102495


Copyright © 2014 Lo Sasso et al. Used by permission.


Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitisassociated 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.

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