Polystyrene nanoplastics promote colorectal tumorigenesis via gut microbiota-metabolite-Th17 cell axis

Nanoplastics (NPs) have emerged as pervasive environmental contaminants, yet their role in colorectal cancer (CRC) pathogenesis remains poorly understood. Here, we demonstrate that chronic oral exposure to polystyrene nanoplastics (PS-NPs) promotes colorectal tumorigenesis in a murine azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC model through disruption of the gut microbiota–metabolite–immune axis. Mechanistically, PS-NPs accumulate predominantly in the colon and cause structural damage to intestinal epithelial microvilli. PS-NPs induce gut microbiota dysbiosis characterized by depletion of the beneficial bacterium Faecalibaculum rodentium ( F. rodentium ) and a consequent reduction in its protective metabolite, propionic acid. This metabolic perturbation attenuates Th17 cell differentiation and IL-17 A production, thereby impairing anti-tumor immunity. Clinically, we detected diverse microplastics in CRC patient tissues and blood. Collectively, our multi-omics and functional analyses delineate a mechanistic pathway linking environmental NPs exposure to colorectal carcinogenesis via the F. rodentium –propionic acid–Th17 cell axis, highlighting the gut microbiome and its metabolites as potential targets for intervention against pollution-associated cancer risks.