Systems toxicology of a tire-wear pollutant: Multi-omics evidence for bioenergetic reprogramming in freshwater clams
The increasing release of tire-derived transformation products into aquatic ecosystems has raised significant environmental concerns, particularly regarding 6PPD-quinone (6PPDQ), a highly toxic compound formed from a widely used tire antioxidant. Despite growing attention, its chronic effects and underlying mechanisms in benthic invertebrates remain poorly understood. This study investigates the systemic impacts of environmentally relevant concentrations of 6PPDQ on the freshwater bivalve Corbicula fluminea using an integrated multi-omics and physiological framework. A 21-day exposure experiment was conducted at concentrations of 4, 8, and 16 ug L-1 alongside a control. Microbial community dynamics were assessed through 16S rRNA and ITS2 sequencing, while host responses were evaluated using RNA sequencing and untargeted LC-MS metabolomics. Co-occurrence network analysis enabled integration of microbiome, transcriptome, and metabolome datasets, revealing key interaction networks and functional pathways. Additionally, oxidative stress biomarkers and histopathological analyses provided evidence of physiological and tissue-level damage. Overall, this study offers a comprehensive systems-level understanding of 6PPDQ toxicity, contributing to improved ecological risk assessment of emerging tire-derived pollutants in freshwater environments.