The potential mechanism of BPF-induced neurotoxicity in adult zebrafish: Correlation between untargeted metabolomics and gut microbiota

Bisphenol F (BPF) is becoming the main substitute for bisphenol A (BPA) in plastics for food and beverage applications. Previous studies have demonstrated the neurotoxicity of BPF; however, its lifecycle toxicity and the underlying mechanisms remain poorly understood. In the current study, zebrafish were continuously exposed to BPF for four months from the embryo to adult stages in order to assess its neurotoxicity. Locomotor behaviors significantly decreased after BPF exposure, which was accompanied by a decrease in body weight, length, and hatching rate. Additionally, BPF increased the expression of inflammatory genes in the brain and destroyed the zebrafishes' intestinal integrity. Meanwhile, the 16S rRNA gene sequence results showed a significantly decreased microbiota abundance and diversity following BPF treatment. Neurotransmitter metabolites were also altered by BPF. Notably, the correlation analysis between microbiota and neurotransmitter metabolism verified that gut microbiota dysbiosis was closely related to the disturbance of neurotransmitter metabolites. Therefore, the present study evaluated the neurotoxicity of lifecycle exposure to BPF and unraveled a novel mechanism involving disturbance of neurotransmitter metabolism and gut dysbiosis, which may provide potential targets for BPF-mediated neurotoxicity.