Microplastics (MPs) have become a significant concern for their potential toxicity. However, the correlation between the size of plastic particles and their toxicity remains inconclusive. Here, we investigate the toxic effects of different sizes (80 nm, 800 nm, 8 µm and 80 µm) polystyrene MPs (PS-MPs) on the model organism Nile tilapia (Oreochromis niloticus). The results of bioluminescent imaging indicate that the 80 nm PS-MPs are more likely to invade the body. H&E staining shows severe damage on the intestinal villi and distinct hepatic steatosis in the 80 nm group. EdU labeling shows that the proliferation activity of intestinal and liver cells reduces significantly in the 80 nm group. The gut microbiome analysis shows a severe imbalance of gut microbiota homeostasis in the 80 nm group. The analysis of liver transcriptomics and metabolomics shows that the liver lipid metabolism is disordered in the 80 nm group. In conclusion, this study confirms that the 80 nm PS-MPs are more likely to induce intestinal and liver toxicity. All the above lay the foundation for further study on the pathological damage of MPs to other organisms.

微塑料（MP）因其潜在毒性而成为人们关注的焦点。然而，塑料颗粒的尺寸与其毒性之间的相关性仍然没有定论。在这里，我们研究了不同尺寸（80 nm、800 nm、8 µm 和 80 µm）聚苯乙烯 MP（PS-MP）对模式生物尼罗罗非鱼（Oreochromis niloticus）的毒性作用。生物发光成像结果表明80 nm PS-MPs更容易侵入体内。H&E 染色显示 80 nm 组肠绒毛严重损伤和明显的肝脂肪变性。EdU标记显示80 nm组肠细胞和肝细胞的增殖活性显着降低。肠道微生物组分析显示，80 nm 组肠道微生物群稳态严重失衡。肝脏转录组学和代谢组学分析显示，80 nm组肝脏脂质代谢紊乱。总之，本研究证实 80 nm PS-MP 更有可能诱发肠道和肝脏毒性。这些为进一步研究MPs对其他生物的病理损伤奠定了基础。