Insecticide and pathogens co-exposure induces histomorphology changes in midgut and energy metabolism disorders on Apis mellifera

Honey bees in agroecosystems face increasingly exposure to multiple stressors, such as pesticides and pathogens, making it crucial to assess their combined impacts rather than focusing on individual factors alone. This study examined the adverse effects of single exposure acetamiprid, Varroa destructor, and Nosema ceranae, both individually and in combination, on honey bee survival, midgut integrity and transcriptomic changes to understand the molecular mechanisms involved. The findings revealed that combination of acetamiprid and N. ceranae induced significant energetic stress, as evidenced by disruptions in energy metabolism. The synergistic effects of V. destructor and N. ceranae led to severe alterations in midgut histomorphology, particularly damaging the midgut epithelium. Concurrent exposure to acetamiprid and V. destructor inhibited the immune response and energy metabolism of honey bees, thereby exacerbating the vulnerability to pathogens and destabilizing their physiological equilibrium. The combination of all three stressors caused the most dramatic damage, disrupting midgut structure as well as aromatic amino acids and lipid metabolism. Our study underscored the complexity and unpredictability of stressor interactions, emphasizing the need to consider environmental context when assessing the risks of honey bee health.