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

Giuseppe Lo Sasso, Dongryeol Ryu, Laurent Mouchiroud, Samodha C. Fernando, Christopher L. Anderson, Elena Katsyuba, Alessandra Piersigilli, Michael O. Hottiger, Kristina Schoonjans, Johan Auwerx

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere102495
JournalPloS one
Volume9
Issue number7
DOIs
StatePublished - Jul 11 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Lo Sasso, G., Ryu, D., Mouchiroud, L., Fernando, S. C., Anderson, C. L., Katsyuba, E., Piersigilli, A., Hottiger, M. O., Schoonjans, K., & Auwerx, J. (2014). Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer. PloS one, 9(7), [e102495]. https://doi.org/10.1371/journal.pone.0102495