Multi-omics analysis reveals the synergistic and intergenerational toxicity of Cr(VI) and chlorfenapyr on zebrafish: disruption of gut-liver axis and mitochondrial impairment

Concurrent hexavalent chromium [Cr(VI)] and chlorfenapyr contamination in aquatic environments poses risks to environmental organisms. A parental zebrafish ( Danio rerio ) exposure model with multi-omics analyses was used to elucidate molecular and transgenerational effects. Combined exposure decreased intestinal tight junction transcription ( zo-1 , and occludin ), caused morphological damage, and activated pro-inflammatory cytokines ( il-1β , il-6 , il-8 , and TNF-α ). 16S rRNA sequencing revealed reduced butyrate-producing bacteria (e.g., Coprococcus ), while untargeted metabolomics showed declines in phospholipid precursors (choline, and glycerophosphocholine), implicating disrupted gut barrier metabolism. Hepatic transcriptomics identified downregulation of oxidative phosphorylation components ( atp5l , atp5mc3b , atp5po , and ndufs7 ) and antioxidant enzymes ( gpx , and mn-sod ), correlating with decreased ATP, mitochondrial membrane potential, and increased apoptosis. F₁ offspring exhibited aberrations in gene transcriptions associated with oxidative phosphorylation and inflammation, suggesting the presence of intergenerational toxicity. These results highlighted the gut-liver axis and mitochondrial function as targets for molecular biomarkers and inform eco-safety regulation addressing chemical mixture hazards.