Size- and vehicle-dependent gut–liver toxicity of tire wear particles in zebrafish

Tire wear particles (TWP) are emerging micropollutants, yet their vehicle type- and particle size-dependent toxicological effects remain inadequately understood. This study systematically evaluated the impacts of TWPs from small-duty and heavy-duty vehicles with varying particle sizes on zebrafish by integrating gut microbiota profiling, hepatic transcriptomics, oxidative stress markers, and physiological traits. Heavy-duty TWPs, especially small-sized particles (SHTWP), induced the most severe effects, including reduced growth, increased oxidative stress, and gut dysbiosis marked by Proteobacteria enrichment and Fusobacteriota depletion. Microbial functional predictions indicated enhanced xenobiotic degradation and energy metabolism, particularly in the SHTWP and LHTWP groups. Hepatic transcriptomics revealed broad activation of detoxification and metabolic stress pathways. Weighted gene co-expression network analysis (WGCNA) identified a turquoise module enriched in detoxification-related genes such as ugt5b4 and nat8 , significantly associated with microbial and host stress traits. Pathway enrichment further highlighted cytochrome P450 and glutathione-related metabolism, indicating a coordinated liver–gut detoxification response. These findings provide mechanistic insight into how TWP characteristics shape toxicological outcomes and underscore the need for size- and type-resolved ecological risk assessments. This work advances our understanding of micropollutant-induced host-microbiome disruption and supports targeted environmental management strategies for non-exhaust vehicular emissions.