Genome-Scale Metabolic Modelling of the <i>Drosophila Melanogaster</i> Gut Microbial Community Uncovers Growth Promoting Metabolite Exchange

Abstract

Most if not all multicellular organisms are inhabited by a vast number of microorganisms, the so-called microbiome. The bacteria present in the digestive system are usually the most abundant microbiome members and important for various aspects of the hosts’ physiology. On top of making food components accessible, microbiome members produce e.g. micronutrients required by the host as well as metabolites, which affect several of the hosts’ signaling pathways. A lot of knowledge exists concerning varying microbiome compositions. How the gut bacteria affect each other, however, remains elusive. In mammals, this is at least in part based on the sheer complexity of the microbiome with hundreds to thousands of different species. Thus, model organisms are commonly used to investigate mechanistic questions. The gut microbiome of Drosophila melanogaster, for example, turned out to be an exquisite model based on its low complexity of only about 10 leading bacterial species in laboratory flies. Here, we isolated abundant gut bacteria from laboratory-reared Drosophila, sequenced their respective genomes and used this information for the reconstruction of genome-scale metabolic models. With these, we simulated growth in mono- and co-culture conditions and different media including a synthetic diet designed to grow Drosophila melanogaster. Our simulations reveal a synergistic growth of some but not all gut microbiome members, which stems on the exchange of distinct metabolites including Tricarboxylic acid cycle intermediates. Culturing experiments confirmed our predictions, thus demonstrating the existence of microbiome-derived prebiotics.