Gut Epithelial Regeneration and the Microbiome: Decrypting Signals in the Crypt

The intestinal crypt represents a strategic niche where signals are integrated to regulate epithelial regeneration, due to the presence of stem cells and their associated lineages such as Paneth cells and proliferative cells of the transit-amplifying compartment. We have selected the intestinal crypt as a model to study microbiota-host cross-talks. Our starting hypothesis was that among the complex assemblage of luminal and mucosal commensal species that compose the microbiota, a limited set may enter into a mutualistic interaction with the cells in the intestinal crypt reflecting a long co-evolution in which the epithelial regenerative apparatus may benefits from microbiota-mediated protection. We are currently developing a cellular microbiology of the intestinal crypt, particularly in the caecum and the colon where we have identified a "crypt specific core microbiota" (CSCM) that is composed of a restricted set of strictly aerobic, non-fermentative microorganisms whose possible function of crypt "gatekeeper" is currently under study. In this context, we have provided the first evidence that a bacterial product, the peptidoglycan fragment muramyl-dipeptide (MDP), exerts a strong and direct NOD2dependant cytoprotective effect on intestinal stem cells upon induction of a cytotoxic stress.