Ingestion of a human-relevant mixture of environmentally sourced microplastics promotes inflammation and tumorigenesis in the mouse colon.

The increasing consumption of plastic in our society has led to the dissemination of microplastics in the environment, which, by diffusing into the food chain and across terrestrial compartments, results in human exposure to a wide diversity of particulate plastics. This study aimed to elucidate the impact of a realistic mixture of microplastics on the colon. Environmental samples composed of the four predominant polymers were cryoground. Irregularly shaped micro-fragments of polypropylene, polyethylene terephthalate, polystyrene, and polyethylene (45-100 μm) were mixed and incorporated into the mouse diet at three doses (5, 50, and 500 μg/g) to reproduce the proportions found in human stool. A 30-day exposure to the microplastic mixture induced dose-dependent alterations of the colonic transcriptome, with downregulation of heat-shock proteins. T-cell activation and cytokine-cytokine receptor interaction signaling pathways were dysregulated at all three doses. This was accompanied by immune dysfunction in the mesenteric lymph nodes. A 30-day exposure worsened the development of colonic inflammation in the DSS-induced colitis model, with increases in the colon weight-to-size ratio, myeloperoxidase activity, and cytokines transcript levels at the medium dose. A 75-day exposure exacerbated tumorigenesis in the AOM/DSS-induced colorectal cancer model at the high dose, as evidenced by worse endoscopic, macroscopic, and histologic scores of tumorigenesis, and increased Cyclin D1 and MYC protein expression. In mice, oral exposure to an environmentally sourced microplastic mixture that reproduces the size, shape, polymer types, and relative proportions of microplastics detected in human stool leads to colonic transcriptomic dysregulation and increased susceptibility to inflammation and tumorigenesis.