Molecular dialogue between intestinal stem cells and microbiota

The intestinal epithelium faces unique challenges as it is constantly exposed to the passage of ingested material including food, bacteria and xenobiotics. To maintain tissue function, the intestinal epithelium is undergoing continuous renewal mediated by intestinal stem cells (ISCs). ISC proliferation and differentiation are constantly adapted both to the microbes present and to the gut environment, suggesting that the structure and composition of the gut epithelium is plastic. Sustained tissue function is essential to organismal health and disruption of gut homeostasis is associated with a broad range of pathologies such as inflammatory disorders and cancer. Despite the central role of ISCs in health and disease, little is known about the molecular mechanisms that regulate ISC activity in response to the microbial environment in the luminal content and how these processes sustain health. Recent results in the Buchon lab have demonstrated that indigenous and invasive gut microbes influence ISC activity. Notably, we have demonstrated that pathogens and non-pathogenic microbes influence the differentiation of ISCs in an opposite way. This project is a collaboration between the Buchon and Sethupathy labs, in which we propose to dissect the molecular dialogue between ISCs and the microbiota using both Drosophila melanogaster and mouse enteroids as models.

This project is a collaboration between the Buchon, and Praveen Sethupathy labs.