The global prevalence and accumulation of plastic waste is leading to pollution levels that cause significant damage to ecosystems and ecological security. Exposure to two concentrations (1 and 5 mg/L) of 500 nm polystyrene (PS)-nanoplastics (NPs) for 14 d was evaluated in Simocephalus vetulus using transcriptome and 16 s rRNA sequencing analyses. PS-NP exposure resulted in stress-induced antioxidant defense, disturbed energy metabolism, and affected the FoxO signaling pathway, causing neurotoxicity. The expression of Cyclin D1 (CCND), glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase (PCK) genes was decreased compared to the control, whereas the expression of caspase3 (CASP3), caspase7 (CASP7), Superoxide dismutase (SOD), Heat shock protein 70 (HSP70), MPV17, and Glutathione S-transferase (GST) genes was increased, thus, suggesting that NP ingestion triggered oxidative stress and disrupted energy metabolism.. PS-NPs were present in the digestive tract of S. vetulus after 14 days of exposure. In addition, the abundance of the Proteobacteria and opportunistic pathogens was elevated after PS-NPs exposure. The diversity and homeostasis of the S. vetulus gut microbiota were disrupted and the stability of intestinal barrier function was impaired. Multiomic analyses highlighted the molecular toxicity and microbial changes in S. vetulus after exposure to NPs, providing an overview of how plastic pollution affects freshwater organisms and ecosystems.
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