GenX-loaded polystyrene microplastics exacerbate intestinal injury in mice via barrier impairment and microbial dysregulation

Microplastics (MPs) have been shown to adsorb per- and polyfluoroalkyl substances (PFAS) and serve as vehicles for their environmental transport. However, the combined intestinal toxicity of MPs and PFAS remains inadequately investigated. This study investigated the intestinal effects of polystyrene microplastics (PS MPs) loaded with perfluoro (2-methyl-3-oxahexanoic acid) (GenX) in a mouse model. Combined exposure to PS MPs and GenX resulted in marked intestinal tissue injury, characterized by elevated levels of pro-inflammatory cytokines and antioxidative enzymes in the colon, alongside impaired intestinal barrier protein expression. 16S rRNA sequencing revealed that co-exposure markedly altered gut microbiota composition, reducing beneficial genera (e.g., Alistipes and Bacillus ) and increasing pathogenic taxa (e.g., Shigella and Desulfovibrio ), while also disrupting microbial network stability. These shifts play an essential role in the synergistic toxicity induced by PS MPs and GenX. Transcriptomic analysis of intestinal tissue indicated enrichment of differentially expressed genes involved in metabolic and digestive processes, with concomitant activation of oxidative stress and immune-related pathways after exposure to PS MPs and GenX. Furthermore, genes associated with inflammatory factors and oxidative stress markers were upregulated. These findings demonstrate that co-exposure to PS MPs and GenX exacerbates intestinal damage compared to PS MPs alone, providing new insights for comprehensive risk assessment of microplastic exposure.