Oxidative Damage and Neurotransmitter Disorder Caused by Bioinsecticide Spinosad on Honeybee Through Multiomics

The natural origin and biodegradable nature of bioinsecticides endow them with promising application potential, yet they are increasingly becoming a class of insecticides that threaten the survival of honeybees. Spinosad, as a major microbial insecticide, has been detected in nectar source plants. Although its negative effects on bees have been reported, its impact on honeybees from the perspective of gut health has not yet been evaluated. This study comprehensively assessed the effects of three concentrations (0.1, 0.25, and 0.5 mg/L) of spinosad on the apparent and gut health of 7 days old adult honeybee workers (Apis cerana). Following two weeks of oral exposure of spinosad, there was no significant decline in honeybee survival or sucrose consumption, and no significant alterations were observed in the midgut microbiota. However, transcriptomic, metabolomic, and their integrated analyses revealed significant increases for oxiglutathione in the glutathione metabolism pathway, and the genes LOC107999471 and LOC133665765 were significantly altered. The antioxidant substance uric acid significantly decreased. They all indicate that spinosad caused oxidative damage to the honeybee midgut. Additionally, the neurotransmitter histamine significantly decreased, suggesting potential interference with feeding behaviors, circadian rhythm etc. in honeybees. Correlation analysis between metabolites and gut microbiota indicated that beneficial Gilliamella and Bombella played a role in maintaining the stability of gut microbiota to spinosad-induced stress. This study comprehensively evaluated the toxicity of spinosad to honeybees from the perspective of gut health, identified key microbes, metabolites, and genes, and provided insights for the protection of non-target insects such as honeybees.