PT - JOURNAL ARTICLE AU - Caleb N. Fischer AU - Eric Trautman AU - Jason M. Crawford AU - Eric V. Stabb AU - Nichole A. Broderick AU - Jo Handelsman TI - Metabolite exchange within the microbiome produces compounds that influence <em>Drosophila</em> behavior AID - 10.1101/066035 DP - 2016 Jan 01 TA - bioRxiv PG - 066035 4099 - http://biorxiv.org/content/early/2016/07/27/066035.short 4100 - http://biorxiv.org/content/early/2016/07/27/066035.full AB - Animals host multi-species microbial communities (microbiomes) whose properties may result from inter-species interactions; however current understanding of host-microbiome interactions is derived mostly from studies in which is it is difficult to elucidate microbe-microbe interactions. In exploring how Drosophila melanogaster acquires its microbiome, we found that a microbial community influences Drosophila olfactory and egg-laying behaviors differently than individual members. Drosophila prefers a Saccharomyces-Acetobacter co-culture to the same microorganisms grown individually and then mixed, a response mainly due to the conserved olfactory receptor, Or42b. Acetobacter metabolism of Saccharomyces-derived ethanol was necessary, and acetate and its metabolic derivatives were sufficient, for co-culture preference. Preference correlated with three emergent co-culture properties: ethanol catabolism, a distinct volatile emission profile, and yeast population decline. We describe a molecular mechanism by which a microbial community affects animal behavior. Our results support a model whereby emergent metabolites signal Drosophila to acquire its preferred multispecies microbiome.