Gut microbiota regulates the brain metabolism of sexually mature drones

ABSTRACT Previous studies have found that gut microbiota and metabolites may be crucial in insect sexual maturation. For example, during sexual maturity, the increased dopamine in the drone’s brain can affect its reproductive behavior, such as flight, mating, and so on. In addition, gut microbiota can affect brain functions such as learning and memory through metabolites. However, it is currently unclear about the changes in gut microbiota during drone sexual maturation and whether they can affect brain function through their metabolites. Thus, we analyzed gut microbiota and brain metabolome in drones during sexual maturation based on multi-omics and identified markers associated with sexual maturation. In addition, we also explored the potential correlation between differentially expressed microorganisms and metabolites before and after sexual maturation. The results showed significant changes in microbes (Lactobacillus, Chaetothyriales, Mortierella, and Entrophospora), and metabolite pathways (glycerophospholipids), with substantial changes. Lactobacillus and Chaetothyriales showed the most significant changes and therefore can be used as marker bacteria in the sexual maturation of drones. In addition, PS (16:0/20:1(11Z)), PE (P-18:0/20:4), and LysoPC (P-18:0/0:0) showed significant differences in the variation of substances, which can be used as markers related to memory in sexually mature drones. This suggests that the intestinal flora of sexually mature drones undergoes substantial changes and has a stronger glycerophospholipid metabolism. Furthermore, microbial-metabolite correlation analysis revealed that Lactobacillus, Aspergillus, Mortierella, and Pleosporales were strongly correlated with PC and PE in the glycerophospholipid metabolic pathway. Therefore, we hypothesize that these four species may affect drones' brain function by influencing glycerophospholipid metabolism, thereby affecting their learning and memory behavior. These findings provide new insights into the interactions between sexual maturation, gut microbes, and brain metabolism in drones.IMPORTANCELearning and memory are essential for drones to mate with the queen, for example, drones need to learn and memorize the sex pheromone of the queen through olfaction to find the queen for mating. However, research in this area is still limited. We investigated the factors affecting learning and memory behaviors in sexually mature drones by analyzing the gut microbiota and brain metabolites of drones of different ages. In this study, we explored the diversity of gut microbiota and changes in brain metabolism during sexual maturation in drones. Through a comprehensive analysis of gut microbiota and brain metabolism in drones, we found that gut microbiota may influence learning and memory in drones by regulating the content of glycerophospholipids in the brain. These findings provide valuable insights into the use of gut microbiota to regulate learning and memory in sexually mature drones and thereby enhance their mating rate with queens.