Oral exposure to micro- and nanoplastics generated from polyethylene terephthalate suppresses acute intestinal damage in vivo.

Micro- and nanoplastics are emerging environmental contaminants with increasing evidence of their presence in human tissues, particularly via oral exposure. However, toxicological assessments often rely on unrealistically high doses of spherical plastic beads, which do not reflect real-world conditions. In this study, micro- and nanoplastics were generated from polyethylene terephthalate (PET-MNPs) by pin-on-microtextured disc system under ultraviolet irradiation, mimicking their natural fragmentation process in the environment. These PET-MNPs exhibit irregular morphologies, closely resembling those of MNPs found in the environment. To assess their biological impact, mice were orally exposed to environmentally relevant doses of PET-MNPs prior to induction of dextran sulfate sodium-induced acute colitis. Contrary to expectations, exposure to PET-MNPs suppressed disease activity during acute colitis. Histological analysis consistently demonstrated that PET-MNPs reduced acute intestinal damage without affecting the recovery phase. Moreover, RNA-seq analysis revealed that PET-MNPs downregulated key inflammatory pathways, including JAK-STAT, NF-κB, cytokine and chemokine signaling, particularly during the acute phase of colitis. These findings indicate that PET-MNPs downregulates acute immune responses in the gut, a site of oral immune tolerance. This is the first in vivo disease model study applying environmentally realistic PET-MNPs, highlighting the complex, non-linear effects of micro- and nanoplastic exposure on intestinal immune regulation.