Not all intestinal epithelial cells are the same. They are compartmentalized through the head-codal axis facing different microenvironments depending on their location (e.g. duodenum, jejunum, ileum, and colon) providing them with different and unique functions. Additionally, intestinal epithelium cells are organized in a very specific manner throughout the crypt-villi axis facing different concentrations of oxygen. In this research axis, we are developing methods to integrate the gut specific microenvironment (e.g. low oxygen or hypoxia) to evaluate how it impacts the metabolic state of intestinal epithelial cells, their differentiation status and their response against pathogens and commensals. We compare how these mechanisms differ between the different GI sections (e.g. duodenum, jejunum, ileum, and colon) to understand why pathogens have section-specific tropism.