Effects of polystyrene nanoplastics and triphenyl phosphate on salamander: Insights from the gut-liver axis

Microplastics and organophosphorus flame retardants are significant environmental contaminants of aquatic ecosystems, yet their impacts on urodele amphibians remains poorly understood. We investigated the individual and combined effects of environmentally relevant concentrations of polystyrene nanoplastics (PS-NPs, 2 mg/L) and triphenyl phosphate (TPhP, 10 μg/L and 100 μg/L) on the gut-liver axis in the salamander species Pachytriton granulosus. 16S rRNA gene sequencing revealed that PS-NPs exposure significantly increased Desulfovibrio abundance which may induce gut inflammation. TPhP exposure caused a dose-dependent decrease in gut microbiota diversity which may disrupt the gut barrier. Co-exposure to PS-NPs and low-dose TPhP complexified the gut microbiota. Metabolomic, histological, and biochemical analyses indicated that exposure to PS-NPs or TPhP may disturb metabolic processes related to oxidative stress and inflammation via the purine metabolism, oxidative phosphorylation, platelet activation, oxytocin, and FoxO signaling pathways. Detoxification-related metabolism was promoted through the lysosome and AMPK signaling pathways. Co-exposure to PS-NPs and TPhP disrupted lipid metabolism via bile secretion, showing antagonistic interactions. Multi-omics correlation analysis suggested that Faecalitalea , Psychrobacter , Clostridium , and Corynebacterium probably modulate oxidative stress, whereas Cetobacterium and Clostridium probably mediate lipid dysregulation. These findings provide new insights into the mechanisms by which nanoplastics and organophosphorus flame retardants interact along the gut-liver axis and highlight their potential health risks to urodele amphibians.