Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer

Authors

Giuseppe Lo Sasso, Ecole Polytechnique Fédérale de Lausanne
Dongryeol Ryu, Ecole Polytechnique Fédérale de Lausanne
Laurent Mouchiroud, Ecole Polytechnique Fédérale de Lausanne
Samodha C. Fernando, University of Nebraska-LincolnFollow
Christopher L. Anderson, University of Nebraska-LincolnFollow
Elena Katsyuba, Ecole Polytechnique Fédérale de Lausanne
Alessandra Piersigilli, Ecole Polytechnique Fédérale de Lausanne, University of Bern
Michael O. Hottiger, University of Zurich
Kristina Schoonjans, Ecole Polytechnique Fédérale de Lausanne
Johan Auwerx, Ecole Polytechnique Fédérale de Lausanne

Date of this Version

2014

Citation

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

Comments

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

Abstract

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 (Sirt1^int-/-) 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.