Gut microbiota-derived butyrate primes systemic immunity in honeybees by mediating lipid metabolic reprogramming

The gut microbiota plays a crucial role in insect immune priming, inducing memory-like response that functionally resembles adaptive immunity confined to vertebrates. While gut microbiota mediates systemic immune activation in insect hemolymph, the mechanisms underlying remote immunoregulation remain largely unknown. Using honeybee gut microbiota as a model, we identified butyrate as a key microbial metabolite coordinating immune-metabolic crosstalk. Butyrate supplementation restored 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 E2 biosynthesis, which is essential for humoral and cellular immune activation. These findings unraveled that the intricate integration of immune and metabolic systems in honeybees is driven by gut-host interactions, a striking convergence found between these social insects and mammals.