# Gut microbiota-derived butyrate primes systemic immunity in honey bees by mediating lipid metabolic reprogramming

## TL;DR

Gut bacteria in honey bees produce butyrate, which boosts their immune system by changing how their bodies process lipids.

## Contribution

The study identifies butyrate as a key microbial metabolite linking gut microbiota to systemic immune activation in honey bees.

## Key findings

- Butyrate supplementation restores immune competence in germ-free honey bees.
- Butyrate activates lipid metabolism in the fat body through G-protein coupled receptor 41 and inhibits histone deacetylases.
- Butyrate-induced lipid changes upregulate prostaglandin E2 biosynthesis, which is crucial for immune activation.

## 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 E2 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.

The intestinal microbiota is shown to play a critical role in immune priming in insects. Here the authors show that microbiota-derived butyrate is linked to the priming of systemic immune responses via lipid metabolic reprogramming in honey bees.