LAUSR

Microplastics (MPs) as widespread contamination pose a high risk for aquatic organisms. However, current understanding of MP toxicity is based on cell population-averaged measurements. Our aim was to gain a comprehensive understanding of the size-dependent effects of polystyrene MPs (PS-MPs) on intestinal cell populations in zebrafish and characterize the interplay of MPs, intestinal cells and intestinal microbiota. Here, we used single-cell RNA sequencing to determine the transcriptome heterogeneity of 12000 intestinal cells obtained from zebrafish exposed to 100-nm, 5-μm and 200-μm PS-MPs for 21 days. Eight intestinal cell populations were identified. Combined with changes in intestinal microbiota, our findings highlight a previously unrecognized endpoint that all three sizes of PS-MPs induced dysfunction of intestinal immune cells (including effects on phagosomes and regulation of immune system processes) and increased the abundance of pathogenic bacteria. However, only 100-nm PS-MPs altered expression of genes related to phagocyte-produced ROS generation and increased mucus secretion by secretory cells. Microsize PS-MPs specifically changed the lysosome (5 μm) and cell surface receptor signaling (200 μm) processes of macrophages. Our findings pinpoint to cell-specific and size-dependent responses to PS-MPs in fish intestine, which can provide a reference for future study directions.