Polystyrene microplastics induce size-dependent multi-organ damage in mice: Insights into gut microbiota and fecal metabolites

Particle size is one of the most important factors in determining the biological toxicity of microplastics (MPs). In this study, we attempted to examine the systemic toxicity of polystyrene MPs of different sizes (0.5 mu m MP1 and 5 mu m MP2) in C57BL/6 J mice. After the mice were given oral gavage of MPs for 8 consecutive weeks, histopathology and molecular biology assays, 16 S rRNA sequencing of the gut microbiota, and untargeted metabolomics were performed. The results showed that MPs were distributed in the organs in a size-dependent manner, with smaller particles demonstrating greater biodistribution. Further analysis indicated that exposure to MPs caused multi-organ damage through distinct toxicity pathways. Specifically, exposure to 0.5 mu m MP1 led to excessive accumulation and induced more serious inflammation and mechanical damage in the spleen, kidney, heart, lung, and liver. However, 5 mu m MP2 led to more severe intestinal barrier dysfunction, as well as gut dysbiosis and metabolic disorder in association with neuroinflammation. These results are helpful in expanding our knowledge of the toxicity of MPs of different sizes in mammalian models.