Plastic products are indispensable in our lives and in society. Unfortunately, they also have a large environmental impact with the effects of the smallest pieces called microplastics (1µm-5mm) and nanoplastics (<1µm) expected to be more profound due to their presumed capacity to migrate through cells. The potential human health risks related to plastic exposure cannot be neglected considering the plethora of plastic products we use in our daily lives. One of the major exposure routes is ingestion (e.g. through plastic bottles). However, the effects of the presence of plastics in our gastro-intestinal tract, are still unclear as research has been focussing on the uptake of polystyrene spherical particles in cells at unrealistically high concentrations. Thus, there is a gap between current results and actual exposure. We hypothesize that both uptake and presence of plastics in our intestines can have an effect on our health, dependent on shape, size, polymer type and concentration. Therefore, this project will study the effect of plastic in our gastrointestinal tract in a holistic way, including the effects of presence of plastic particles (effects on microbiome, mucus layer, epithelial barrier) and uptake (mucus and epithelial cells). The heterogeneity of the plastic particles will be accounted for using in vitro experiments and a modelling approach. Hence, this project will contribute to unravel the human health effects of plastic particles in realistic exposure scenarios.