Human gut-on-chip as an intestinal model to predict compound absorption and toxicity

The small intestine is a crucial component of the digestive system allowing the digestion of food and absorption of nutrients to supply the body with energy to function properly. The complex anatomy and physiology of the human small intestine poses a challenge when defining alternative testing strategies to characterise intestinal absorption and toxicity. In the present thesis, the potential of an alternative in vitro gut-on-chip model with a continuous liquid flow to study intestinal absorption and toxicity was revealed. A glass-based chip was used to culture epithelial cells under the optimized dynamic conditions. Upon morphologic characterization a selected range of model compounds were used for transport studies including 17 dioxin congeners with different physicochemical properties that are well known food contaminants, and selected pharmaceuticals (i.e. antipyrine, ketoprofen, digoxin, amoxicillin) with well-known uptake profiles from traditional static in vitro models and from human in vivo studies. These studies were followed by the comparative gene expression study of cells cultured in the gut-on-chip and in Transwells and human intestinal tissues. Finally, a comparative gene expression study was performed evaluating the effects on gene expression profiles of a nanomaterial (TiO2 and ZnO) exposure in the gut-on-chip versus the Transwell model.