Transgenerational effects of Nanoplastics and bisphenol A on Zebrafish lipid metabolism: Disruption of the gut Microbiota-liver axis via mTOR pathway.

The gut-liver axis is vital for organism health. Nanoplastics (NPs) and bisphenol A (BPA) can harm zebrafish intestines and livers, yet their combined impact on the gut-liver axis and transgenerational effects are unknown. In this study, F0 zebrafish were exposed to NPs and/or BPA for 28 days. Lipid indices of F0, F1, and F2 zebrafish, as well as the developmental indices of offspring, were detected. 16S rRNA sequencing and metabolomics were used to analyze F0 zebrafish gut microbiota and liver metabolites, exploring underlying mechanisms. The mTOR inhibitor Rapa was injected into F0 zebrafish to examine the mTOR pathway's role in lipid disorders caused by NPs and BPA exposure. The results showed that the exposure of F0 generation zebrafish to NPs and BPA led to lipid metabolism disorders in all generations of zebrafish and abnormal development in F1 and F2 zebrafish. Omics analysis revealed that the combined exposure to NPs and BPA significantly exacerbated the gut microbiota disorder in F0 zebrafish. The differential metabolites identified by untargeted metabolomics were enriched in the mTOR signaling pathway. After Rapa intervention, the lipid disorders in each group of F0 zebrafish were improved. In summary, the combined exposure to NPs and BPA may lead to lipid disorders in all generations of zebrafish and abnormal development of offspring by exacerbating the dysregulation of the gut microbiota-liver axis in F0 zebrafish. The results of this study provide mechanistic insights into the transgenerational effects induced by the combined exposure to NPs and BPA.