Polystyrene micro- and nanoplastics in a colitis mouse model – effects on biodistribution, macrophage polarization, and gut microbiome

<title>Abstract</title> The increasing prevalence of inflammatory bowel disease (IBD) and rising pollution from micro-and nanoplastic (MNP) particles has prompted investigations on their potential interconnection. To elucidate the complex relationship between IBD and exposure to MNPs, we induced colitis in mice using dextran sodium sulfate (DSS) and orally administered a mixture of polystyrene (PS) MNPs (diameter 10, 1, and 0.29 µm). These particles enabled a detailed examination of MNP biodistribution, innate immune cell response and gut microbiome alterations under inflammatory conditions. Specifically, the nanosized PS particles predominantly accumulated in the bloodstream and excretory organs, with enhanced accumulation in the inflamed gut/colon. Proteomic analysis of the colon revealed alterations in molecular pathways related to protein transport, metabolism, and immune responses. Specifically, we found macrophage proteome signatures with pro-inflammatory polarization, highlighting the intricate effects of MNPs on inflammation and immune cell behavior. Moreover, MNPs significantly disrupted the gut microbiome, reducing microbial diversity and shifting bacterial populations towards pro-inflammatory and potentially pathogenic species. These changes suggest that MNP exposure could exacerbate colitis through complex interactions involving MNPs, immune responses, and microbial dynamics. The fast-growing exposure to MNPs underscores the urgent need for comprehensive strategies to address MNP pollution, its implications for disease, and potential impacts on public health.