Copper (Cu) is a common contaminant in aquatic environments, which could cause physiological dysfunction in aquatic organisms. However, few studies have comprehensively examined the impact of copper toxicity in freshwater fish over the past decade. In this research, the oxidative stress, liver transcriptome, intestinal microbiota, and histopathology of common carp (C. carpio) in response to Cu exposure were studied, by exposing juvenile carp to 0.2 mg/ml Cu²⁺ for 30 days. The results revealed that Cu²⁺ could induce significant changes in malondialdehyde (MDA) content and antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)) activity. The changes in antioxidant enzyme activities indicate that Cu can induce oxidative stress by generating reactive oxygen species (ROS) content. RNA-seq analysis of the liver identified 1069 differentially expressed genes (DEGs) after treatment with 2.0 mg/L Cu²⁺. Among the DEGs, 490 genes were upregulated and 579 genes were downregulated. GO functional enrichment analysis revealed that Cu could affect the fatty acid biosynthetic process, carnitine biosynthetic process, and activity of carboxylic acid transmembrane transporter. Meanwhile, the most significantly enriched KEGG pathway also included the lipid metabolism pathway. In addition, Cu²⁺ exposure increased bacterial richness and changed bacterial composition. At the phylum level, we found that the ratio of Bacteroidetes to Firmicutes was increased in the treatment carps, which can regulate intestinal epithelium function and reduce inflammation and immune responses. At the genus level, the abundances of 11 genera were significantly altered after exposure to Cu²⁺. The altered composition of the microbial community caused by Cu exposure may play a useful role in compensation of the intestinal lesions by Cu exposure. Furthermore, we found that Cu²⁺ exposure could cause histological alterations such as structural damage to the liver and intestines. The results of this research contribute to a better understanding of mechanisms related to Cu toxicity in fish.

#	Concept	H-Index	Publications	Citations
1	Engineering	1	1	27
2	Medicine	1	1	27
3	Biology	1	1	27
4	Functional Genomics	1	1	27
5	Gene Expression	1	1	27

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