Combined toxicity of nanoplastics and sodium fluoride to zebrafish liver: Impact on gut-liver axis homeostasis and lipid metabolism.

Nanoplastics and fluorides are widespread environmental pollutants, but their combined exposure risks to aquatic organisms and humans remain unclear. Studying their combined effect of inducing toxicity on the gut-liver axis at environmentally relevant concentrations is critical. Using zebrafish, this study evaluated toxic effects and mechanisms of single/combined exposure to 0.1 mg/L nanoplastics (NPs) and 15 mg/L sodium fluoride (NaF). Integrating network toxicology and in vivo validation, combined exposure significantly disrupted intestinal structure, increased permeability, and disturbed microbiota balance. Gut microbiota dysbiosis mediated hepatic lipid metabolism disorders via the gut-liver axis by activating the TLR4/NF-κB pathway, inducing liver inflammation, oxidative stress, and hepatocyte apoptosis. The observed toxic effects are consistent with gut-liver axis homeostasis disruption, though definitive causal links have not been established. This reveals their combined effect of inducing liver injury by interfering with gut-liver axis homeostasis, providing a theoretical basis for assessing ecological risks of compound pollutants and scientific references for pollution management and aquatic ecological protection.