Tire wear particle leachate-induced hepatotoxicity in Carassius auratus: Associations with gut microbiota dysbiosis and lipid metabolism disorder.

Tire wear particles (TWPs), which are increasingly released into aquatic environments, pose a potential threat to aquatic organisms. Clarifying the hepatotoxic effects and mechanisms of TWP leachate is important for aquatic health protection. In this study, crucian carp (Carassius auratus) were exposed to environmentally relevant concentrations of TWP leachate for 28 days to investigate its hepatotoxic effects and potential mechanisms. The results revealed that TWP leachate exposure led to zinc accumulation in the intestine and liver. Additionally, we found that TWP leachate exposure significantly increased the hepatosomatic index, accompanied by hepatic necrosis, inflammatory cell infiltration, weakened antioxidant defense. Meanwhile, TWP leachate exposure induced gut microbiota dysbiosis, as characterized by reduced beneficial bacteria (Lactobacillus, Bacillus, Roseburia) and enriched opportunistic pathogens (Aeromonas, Mycobacterium). Furthermore, TWP leachate exposure also perturbed hepatic glycerophospholipid metabolism, fatty acid degradation, and AMPK/PPAR signaling. Transcriptome sequencing and qPCR analysis demonstrated that TWP leachate suppressed AMPK/PPAR signaling, upregulated lipogenic genes (FAS, ACC1), and activated inflammatory cytokines (TNF-α, IL-1β) in the liver. Collectively, this study suggests that TWP leachate-induced hepatotoxicity was highly associated with gut microbiota dysbiosis and AMPK/PPAR-related disruption of lipid metabolism in crucian carp. Our study provides new mechanistic insights for the ecotoxicological risks posed by chemical mixtures released from TWPs in aquatic ecosystems.