Grant: Project Grant

Injuries to the intestinal epithelium need to be swiftly repaired, otherwise bacteria from the microbiota and potential pathogens could get access to deeper tissues. Recent advances in this field of research have shown that, following injury to the intestinal epithelium, a population of intestinal stem cells rapidly emerges, and contributes to the repair of this epithelium by dividing actively, thereby allowing replacement of the damaged epithelium. Here we have made the unexpected discovery that a specific metabolite from bacteria, known as ADP-Heptose, can boost the emergence of these specific stem cells, which should protect the epithelium following injury. In this project, we propose to dissect how ADP-Heptose promotes the emergence of these cells, using ex vivo models of murine and human intestinal organoids and using in vivo models. Together, this research will advance our understanding of how the epithelium repairs following injury and will reveal the contribution of the intestinal microbiota in this process. This may have clinical implications for chronic inflammatory diseases, such as Crohn's disease, for which alteration of the intestinal barrier is believed to be causative event.