Chronic oral exposure to oxidized polyethylene microplastics induces goblet cell loss and gut microbiota dysbiosis in female mice

Environmental oxidized polyethylene microplastics (Ox-PE-MPs) are an increasing concern due to their altered surface chemistry and potential to disrupt intestinal homeostasis. In this study, we investigated the intestinal effects of UV-oxidized PE microplastics (Ox-PE-MPs; 10–30 µm) orally administered to male and female mice at 500 mg/kg/day for 13 weeks as an exploratory high-dose hazard-identification study. Histopathological analysis revealed a significant reduction in colonic goblet-cell numbers in female mice. Moreover, 16S rRNA gene sequencing demonstrated reduced gut microbial diversity and altered microbial composition, including increased relative abundances of Proteobacteria and Desulfobacterota. These histological and microbial changes occurred concurrently in female mice, whereas male mice did not exhibit comparable alterations. Because both endpoints were evaluated at the terminal time point, their temporal sequence and causal relationship could not be determined. These findings provide preliminary evidence of sex-dependent intestinal responses to repeated high-dose exposure to Ox-PE-MPs. Because the administered dose exceeds expected environmental exposure levels, the results should be interpreted as hazard-identification evidence rather than as a direct estimate of human environmental risk.