Evaluation of intestinal toxicity of polystyrene micro/nanoplastics using intestinal organoids

Polystyrene micro/nanoplastics (PS-MNPs) have emerged as a growing threat to human health, with oral ingestion representing a major route of exposure. Although their distribution and adverse effects in animal gastrointestinal tract have been extensively investigated, their specific impact on the human intestine, particularly on epithelial maturation, remains largely unknown. Here, human intestinal organoids (HIOs) were employed to elucidate the toxicity mechanisms of PS-MNPs. The results demonstrated that PS-MNPs accumulated within HIOs, where they not only induced mitochondrial membrane potential reduction, reactive oxygen species level elevation and DNA integrity destruction, but also disrupted proliferation and differentiation of intestinal epithelial cells by downregulating key regulators of the cell cycle and DNA replication. Ultimately, these combined effects impaired epithelial self-renewal, maturation and function. Notably, PS-MNPs showed size-dependent toxicity, with the nanoscale particles exhibiting higher internalization and stronger toxicity compared to the microscale counterparts. Overall, our study unveils a mechanistic basis for MNP-induced intestinal toxicity, and provides new insights into their potential contribution to intestinal barrier dysfunction and chronic intestinal disorders in humans.