Abstract

The gut microbiota plays a crucial role in insect immune priming, inducing enhanced immune response that functionally resembles acquired immunity confined to vertebrates. While gut microbiota mediates systemic immune activation in insect hemolymph, the mechanisms underlying remote immunoregulation remain largely unknown. Here we use the honey bee gut microbiota as a model, we identify butyrate as a key microbial metabolite coordinating immune-metabolic crosstalk. Butyrate supplementation restores immune competence in germ-free bees, mirroring the protective effects of microbiota-colonized individuals. Butyrate orchestrates lipid metabolic reprogramming in the fat body by activating glycerolipid and arachidonic acid metabolism through activating the G-protein coupled receptor 41 while inhibiting histone deacetylases. These changes in-turn upregulate prostaglandin E 2 biosynthesis, which is essential for humoral and cellular immune activation. These findings unravel how the intricate integration of immune and metabolic systems in honey bees is driven by gut-host interactions.