Using human iPSC derived small intestinal organoids as a model for enteric disease caused by Enterotoxigenic E. coli and Vibrio cholerae

Within the last ten years, iPSC (induced pluripotent stem cells) have been widely shown to have the ability to be re-programmed to produce a wide range of tissues in the presence of certain growth factors. In this project, we re-direct human stem cells derived from fibroblasts into complex 3D small intestinal structures termed organoids. These organoids have been shown to possess all cell types that are present in small intestinal tissue such as, enterocytes, goblet cells, enteroendocrine cells and Paneth cells, as well as possessing microvilli and crypt structures. We demonstrate that it is possible to microinject into the lumen of these small intestinal organoids and to manipulate the conditions for infection of non-invasive bacteria such as Enterotoxigenic E. coli (ETEC) and Vibrio cholerae . Looking at known bacterial virulence factors, we have shown there are differences in patterns of infection among different strains of entero-pathogenic bacteria. In addition, we have shown that the induced human organoids (iHO) elicit a recognisable and measurable host response to bacterial toxin.