Toxicity and absorption of polystyrene micro-nanoplastics in healthy and Crohn's disease human duodenum-chip models

Micro and nanoplastics (MNPs) are widespread environmental and food web contaminants that are absorbed by the intestine and distributed systemically, but the mechanisms of uptake are not well understood. In a triculture small intestinal epithelial model, we previously found that uptake of 26 nm polystyrene MNPs (PS26) occurred by both passive diffusion and active actin- and dynamin-dependent mechanisms. However, studies in a more physiologically relevant model are required to validate those results. Here, a microfluidic intestine-on-a-chip model was developed using primary human intestinal epithelial organoids from healthy and Crohn's disease donors, and used to evaluate the toxicity and mechanisms effectuating uptake of 25 nm polystyrene shell-gold core tracer MNPs (AuPS25). AuPS25 caused minimal toxicity after 24 h exposure in either healthy or Crohn's IOC models. RNAseq analysis of epithelial cells identified 9 genes dysregulated by AuPS25, including downregulation of IFI6 (interferon alpha-induced protein 6). Because IFI6 has important antiviral and immunosuppressive functions in the intestine, its downregulation suggests impairment of innate immune function, which could have important negative health consequences. Inhibitor studies revealed that AuPS25 uptake in the IOC occurred by both passive diffusion and active actin- and dynamin-dependent mechanisms, consistent with our previous findings in the triculture model.