Drosophila and its gut microbes: a model for drug-microbiome interactions

Drosophila is an excellent system to investigate how the presence and composition of the gut microbiome influences the efficacy of therapeutic drugs and downstream consequences for host health. These opportunities derive from two key attributes of Drosophila. First, Drosophila is amenable for microbiome research, with simple, standardized methods to produce large numbers of microbiologically-sterile flies and flies with a standardized gut microbiome, thereby facilitating experimental reproducibility. Second, Drosophila is a well-established genetic model that is increasingly used to elucidate the molecular and physiological basis of lesions associated with human disease alleles; this provides the opportunity to link microbiome/drug interactions to previously-described processes shaping health and disease. In this way, Drosophila can fast-track understanding of fundamental biology to generate precise hypotheses for testing in mammalian systems. Drosophila is particularly well-suited to investigate the incidence of microbiome/drug interactions mediated by different mechanisms, including microbial drug metabolism (to active, inactive or toxic derivatives), microbial production of compounds that inhibit drug efficacy, and off-target effects of the drug on the microbiome, resulting in dysbiosis and host ill-health. Drosophila can also be used to investigate how interactions between the microbiome and host genotype may shape responses to therapeutic drugs, informing the reliability of precision medicine based exclusively on human genomic markers.