Investigation of the mechanisms of liver injury induced by emamectin benzoate exposure at environmental concentrations in zebrafish: A multi-omics approach to explore the role of the gut-liver axis.

Emamectin benzoate (EMB) is a lipophilic pesticide that enters aquatic systems and adversely affects non-target organisms. This study investigated the long-term effects of EMB on zebrafish, exposing them to concentrations of 0, 0.1, 1, and 10 μg/L from the 4-hour post-fertilization (hpf) embryo stage to the 120-day post-fertilisation (dpf) adult stage. We found that exposure to 1 μg/L EMB induced liver damage, manifested as impaired liver function (elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), histopathological damage (lipid accumulation), as well as inflammatory and oxidative damage, with a dose - dependent effect. Non-targeted metabolomic analysis revealed an increase in lipid molecules in the liver, affecting the pathways related to glycerophospholipid metabolism. In addition, EMB exposure resulted in damage to the intestinal barrier and inflammatory responses in zebrafish. 16S rRNA sequencing demonstrated that EMB exposure resulted in notable alterations in the gut microbiota composition. Notably, the abundance of Plesiomonas and Cetobacterium increased in the EMB exposure group and exhibited a positive correlation with the majority of liver lipid metabolites. In contrast, reductions in Muribaculaceae and Alloprevotella were negatively correlated. The results of this study indicate that long-term exposure to EMB disrupts the gut microbiota, leading to the dysregulation of hepatic phospholipid metabolism. These findings provide new insights into the health risks associated with EMB and highlight its potential threats to higher organisms, including mammals.