The role of gut microbiota in mediating increased toxicity of nano-sized polystyrene compared to micro-sized polystyrene in mice

Microplastics (MPs) are widespread environmental contaminants that have been detected in animals and humans. However, their toxic effects on terrestrial mammals and the underlying mechanisms are still not well understood. Herein, we explored the role of gut microbiota in mediating the toxicity of micro- and nano-sized polystyrene plastics (PS-MPs/PS-NPs) using an antibiotic depleted mice model. The results showed that PS-MPs and PS-NPs exposure disrupted the composition and structure of the gut microbiota. Specifically, these particles led to an increase in pathogenic Esherichia-shigella, while depleting probiotics such as Akkermansia and Lactobacillus. Comparatively, PS-NPs particles had more pronounced effect, leading to obviously shifted the colon transcriptional profiles characterized by inducing the enrichment of colon metabolism and immune- related pathways (i.e., upregulated in genes like udgh, ugt1a1, ugt1a6a, ugt1a7c and ugt2b34). Additionally, both PS-MPs and PS-NPs induced oxidative stress, gut-liver damage and systemic inflammation in mice. Mechanistically, we confirmed that PS particles disturbed gut microbiota, activating TLR2-My88-NF-κB pathway to trigger the release of inflammatory cytokine IL-1β and TNF-α. The damage and inflammation caused by both size of PS particles was alleviated when the gut microbiota was depleted. In conclusion, our findings deepen the understanding of the molecule mechanisms by which gut microbiota mediate the toxicity of PS particles, informing health implications of MPs pollution.