Ethanol consumption mediates parasitoid resistance via effects on host metabolism

Many insect species use self-medication, the consumption of an environmental compound with antipathogen activity, as a defense against pathogen infection. One well-studied example is the interaction between Drosophila melanogaster and parasitoid wasps, in which D. melanogaster larvae consume ethanol-laden food to kill the developing parasitoid. Despite research into self-medication as a behavioral immune response to parasitoid infection, the parasitoid-killing mechanism remains elusive. To test the impact of ethanol consumption and infection on host metabolism, we used untargeted Nuclear Magnetic Resonance (NMR) metabolomics of hemolymph samples isolated from naive and parasitoid infected larvae fed ethanol-containing or control food. Surprisingly, we found that the consumption of dietary ethanol did not result in an elevated hemolymph ethanol abundance. Instead, we found evidence that host carbohydrate-derived energy production and amino acid metabolism were altered by ethanol consumption. Our results suggest that these ethanol-mediated changes in host metabolism, rather than a direct effect of dietary ethanol, confers parasitoid resistance.