Infected Fruit Flies Self-Medicate through Macronutrient Selection to Optimise Fitness

Animals manipulate their environment to reduce the impacts of biotic and abiotic stresses, including infection. One of the most intimate interactions animals have with their environment is their diet, although we know surprisingly little about how animals alter their intake and excretion during pathogenic encounters, and whether these changes are beneficial to the host’s physiology or fitness. Illness-induced anorexia, i.e. eating less in response to infection,is one of the most commonly observed behaviours following infection. Although known to be a host-driven response, how this counter-intuitive strategy benefits the animal remains strongly debated with many suggesting it is employed to limit the ingestion of harmful toxins or micronutrients. In this study, we utilise chemically-defined (holidic) diets in a nutritional geometric framework to assess the independent contribution of micronutrients, macronutrients, and calories to the fitness of the infected fruit fly, Drosophila melanogaster,as well as to identify their dietary preference following a pathogenic encounter. We find female flies facing a natural fungal infection require a lower-calorie, protein-rich diet to maximise both their survival and life reproductive fitness relative to healthy individuals. Furthermore, we identify that flies facing pathogen encounters alter their dietary preference towards this optimum, and that both chosen elements of calorie-content, and macronutrient ratio limit in vivo microbe growth. Finally we show that flies excrete more protein, but not carbohydrates during infection, which we argue is a pathogen-driven manipulation of the host. Overall, our results demonstrate the first conclusive evidence that flies self-medicate to optimise fitness through macronutrient selection.