Lo Sasso, GiuseppeGiuseppeLo SassoRyu, DongryeolDongryeolRyuMouchiroud, LaurentLaurentMouchiroudFernando, Samodha CSamodha CFernandoAnderson, Christopher LChristopher LAndersonKatsyuba, ElenaElenaKatsyubaPiersigilli, AlessandraAlessandraPiersigilliHottiger, Michael OMichael OHottigerSchoonjans, KristinaKristinaSchoonjansAuwerx, JohanJohanAuwerx2024-10-232024-10-232014https://boris-portal.unibe.ch/handle/20.500.12422/131657Dysfunction 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.en600 - Technology::630 - Agriculturearticle10.7892/boris.663882501393010.1371/journal.pone.0102495