AbstractMicroplastics (MPs) are a widely recognized global problem due to their prevalence in natural environments and the food chain. However, the impact of microplastics on human microbiota and their possible biotransformation in the gastrointestinal tract have not been well reported. To evaluate the potential risks of microplastics at the digestive level, completely passing a single dose of polyethylene terephthalate (PET) through the gastrointestinal tract was simulated by combining a harmonized static model and the dynamic gastrointestinal simgi model, which recreates the different regions of the digestive tract in physiological conditions. PET MPs started several biotransformations in the gastrointestinal tract and, at the colon, appeared to be structurally different from the original particles. We report that the feeding with microplastics alters human microbial colonic community composition and hypothesize that some members of the colonic microbiota could adhere to MPs surface promoting the formation of biofilms. The work presented here indicates that microplastics are indeed capable of digestive-level health effects. Considering this evidence and the increasing exposure to microplastics in consumer foods and beverages, the impact of plastics on the functionality of the gut microbiome and their potential biodegradation through digestion and intestinal bacteria merits critical investigation.