The project aims to establish a model of the intestine barrier based on human induced pluripotent stem cells (hiPSCs), using a temporal series of growth factors mimicking embryogenic intestinal development. As iPSCs can be efficiently directed to differentiate into human intestinal organoids, acquiring both absorptive and secretory functions, the model will be used to investigate the epithelial barrier function following a number of insults, including metabolic dysregulation, oxidative stress, micro- and nanoplastics, persistent chemicals. With an eye on upscaling, microfabrication approaches (e.g., microwell arrays) will be sought to augment reproducibility of organoid formation. A set of readout protocols, largely relying on high-content microscopy and AI-based segmentation and feature extraction methodologies will be optimized, to develop a phenotypic drug screening platform for the identification of novel therapeutic strategies.