Microbiome-by-ethanol interactions impact Drosophila melanogaster fitness, physiology, and behavior.

The gut microbiota can affect how animals respond to ingested toxins, such as ethanol, which is prevalent in the diets of diverse animals and often leads to negative health outcomes in humans. Ethanol is a complex dietary factor because it acts as a toxin, behavioral manipulator, and nutritional source, with both direct effects on the host as well as indirect ones through the microbiome. Here, we developed a model for chronic, non-intoxicating ethanol ingestion in the adult fruit fly, , and paired this with the tractability of the fly gut microbiota, which can be experimentally removed. We linked numerous physiological, behavioral, and transcriptional variables to fly fitness, including a combination of intestinal barrier integrity, stored triglyceride levels, feeding behavior, and the immunodeficiency pathway. Our results reveal a complex tradeoff between lifespan and fecundity that is microbiome-dependent and modulated by dietary ethanol and feeding behavior.