Tire-wear particle leachate at environmentally relevant concentrations exert a hepatotoxic impact on the black-spotted frog by disrupting the gut–liver axis

As global surface water pollutants, tire-wear particles (TWPs) are increasingly concerning, with TWP leachate hepatotoxicity poorly understood. In this study, based on environmental TWP concentrations, TWP leachate exposure (0, 0.0005, 0.005, 0.05, and 0.5 mg/mL) in black-spotted frogs was investigated over a 21 day period. TWP leachates at realistic environmental levels disturbed intestinal microbiome homeostasis, which manifested as decreased and increased Chloroflexi and Proteobacteria abundance, respectively, and elevated lipopolysaccharide (LPS) levels in plasma. Also, the content of lipopolysaccharide-binding protein, the binding site of LPS, was increased, and downstream LPS immune pathways, such as toll-like receptor 4 (TLR4)-nuclear factor (NF)-κB (TLR4/NF-κB) signaling, were activated. Subsequently, inflammation reactions, oxidative damage, and histopathology were affected in liver samples. These results shed new light on the potential mechanisms underpinning TWP leachate-associated liver injury via the gut–liver axis, and contribute to a better understanding of emerging TWP ecotoxicology.