Toxicity of true-to-life microplastics to human iPSC-derived intestinal epithelia correlates to their protein corona composition

Humans are continually exposed to microplastics, now pervasive in the environment. The intestinal epithelium, as a primary barrier tissue, frequently faces high microplastic exposure, yet health implications remain elusive. Using an intestinal epithelial cell model derived from human induced pluripotent stem cells, we show intestinal toxicity upon exposure to true-to-life polyethylene terephthalate-TiO 2 , polypropylene-Talc, polyvinyl chloride and polyamide microplastics. These materials compromised barrier integrity, elevated intracellular reactive oxygen species and stimulated intestinal cytokine secretion. Epithelial perturbations were not observed upon exposure to polystyrene microplastics, which frequently serve as a proxy for product-derived microplastic exposure. Proteomics analysis identified unique protein corona compositions for each microplastic, which correlated with in vitro effects. For example, the abundance of biocorona proteins involved in inflammation strongly correlated to the degree of cytokine secretion. These findings underscore the need for routine availability of true-to-life microplastics and protein corona analysis in hazard assessment to enable safe-by-design plastic development.