Bacterial Metabolism and Transport Genes Are Associated with the Preference of Drosophila melanogaster for Dietary Yeast.

Many animal traits are influenced by their associated microorganisms ("microbiota"). To expand our understanding of the relationship between microbial genotype and host phenotype, we report an analysis of the influence of the microbiota on the dietary preference of the fruit fly Drosophila melanogaster. First, we confirmed through experiments on flies reared bacteria-free ("axenic") or in monoassociation with two different strains of bacteria that the microbiota significantly influences fruit fly dietary preference across a range of ratios of dietary yeast:dietary glucose. Then, focusing on microbiota-dependent changes in fly dietary preference for yeast (DPY), we performed a metagenome-wide association (MGWA) study to define microbial species specificity for this trait and to predict bacterial genes that influence it. In a subsequent mutant analysis, we confirmed that disrupting a subset of the MGWA-predicted genes influences fly DPY, including for genes involved in thiamine biosynthesis and glucose transport. Follow-up tests revealed that the bacterial influence on fly DPY did not depend on bacterial modification of the glucose or protein content of the fly diet, suggesting that the bacteria mediate their effects independent of the fly diet or through more specific dietary changes than broad ratios of protein and glucose. Together, these findings provide additional insight into bacterial determinants of host nutrition and behavior by revealing specific genetic disruptions that influence D. melanogaster DPY. Associated microorganisms ("microbiota") impact the physiology and behavior of their hosts, and defining the mechanisms underlying these interactions is a major gap in the field of host-microbe interactions. This study expands our understanding of how the microbiota can influence dietary preference for yeast (DPY) of a model host, Drosophila melanogaster. First, we show that fly preferences for a range of different dietary yeast:dietary glucose ratios vary significantly with the identity of the microbes that colonize the fruit flies. We then performed a metagenome-wide association study to identify candidate bacterial genes that contributed to some of these bacterial influences. We confirmed that disrupting some of the predicted genes, including genes involved in glucose transport and thiamine biosynthesis, resulted in changes to fly DPY and show that the influence of two of these genes is not through changes in dietary ratios of protein to glucose. Together, these efforts expand our understanding of the bacterial genetic influences on a feeding behavior of a model animal host.