Gut microbiota and metabolic disruption induced by food chain-transferred nanoplastics: A mediating role of CYP26A1 in retinoic acid toxicity

Polystyrene nanoplastics (PS-NPs) pollution has emerged as critical environmental and public health concerns due to their potential for bioaccumulation and systemic toxicity. While our previous work demonstrated the trophic transfer of micro- and nanoplastics from insect yellow mealworms (Tenebrio molitor) to mammals, the biological consequences remain poorly understood. This study aimed to investigate the impact of food chain-transferred PS-NPs (FCT-NPs) on the gut-liver axis in a mouse model. We demonstrate that FCT-NPs induce gut microbiota dysbiosis, disrupt metabolic homeostasis, and alter hepatic gene expression in mice. Crucially, we identify the upregulation of Cyp26a1 gene underlying FCT-NPs-induced hepatoxicity, which interferes with retinoic acid metabolism and leads to hypervitaminosis A. By elucidating the molecular link between gut microbial shifts and hepatic dysfunction, this study highlights gut-liver axis as a primary target of FCT-NPs and lays the foundational insights into their broader systemic ecological and physiological consequences.