Integrated analysis of zebrafish gut microbiota and liver transcriptome responses to polystyrene microplastics and cadmium

Microplastics (MPs) and cadmium (Cd) are pervasive pollutants in aquatic ecosystems, yet their combined toxicological effects remain poorly understood. Therefore, to understand the toxicological interactions between MPs (5-μm polystyrene) and Cd, we investigated gut microbial and hepatic transcriptome regulation in zebrafish ( Danio rerio ) following single and combined exposure to MPs and Cd. The 16S rRNA gene sequencing analysis of the gut microbiota in zebrafish revealed that PS-MPs exposure decreased the relative abundance of probiotics and increased the abundance of conditionally pathogenic bacteria. The transcriptome analysis of zebrafish was then performed to reveal the molecular mechanism of the response to MPs and Cd. In total, a total of 8530, 3778 and 11,048 differentially expressed genes were identified in the PS-MPs group, Cd group and composite group respectively. The results of GO and KEGG pathway analysis of the DEGs identified cytochrome P450 drug metabolism-related and oxidative stress-related pathways. In conclusion, chronic exposure to PS-MPs and Cd disrupted the gut microbial community structure and reprogrammed hepatic transcriptional responses in zebrafish, with the combined exposure eliciting a broader and more pronounced shift than either stressor alone. Notably, the enrichment of opportunistic/pathogenic taxa occurred alongside the suppression of hepatic xenobiotic metabolism and antioxidant-related pathways (e.g., CYP450- and GST-associated processes), consistent with a pollutant-driven perturbation of gut-liver homeostasis. These findings provide a dual-omics view of PS-MPs-Cd co-exposure and highlight the potential involvement of the gut-liver axis, warranting further validation with functional endpoints. • Synergistic PS-MPs and Cd exposure induces more severe gut microbiota dysbiosis in zebrafish than individual treatments. • Co-exposure impairs hepatic detoxification by downregulating CYP450 and GST enzymes. • Analysis links gut pathogens Aeromonas/Cetobacterium to hepatic detoxification/inflammation genes. • Study reveals gut-liver axis role in MP-modulated Cd toxicity, providing a multi-omics framework for aquatic assessment.