Biological Sciences Faculty Work
Predicted Metabolic Function of the Gut Microbiota of Drosophila melanogasterAn important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and their impact on host physiology. This research can be confounded by poorly understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multiway interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the Drosophila gut microbiome (from single taxa to the five-member community of Acetobacter and Lactobacillus species) under three nutrient regimes. We show that the metabolic function of Drosophila gut bacteria is dynamic, influenced by community composition, and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that, in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle, including 2-oxoglutarate and succinate, are produced at high flux and cross-fed between bacterial taxa, suggesting important roles for TCA cycle intermediates in modulating Drosophila gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the host.
Succinate: a microbial product that modulates Drosophila nutritional physiologyGut microorganisms process food in animal guts and release many metabolic by-products, which are predicted to influence host physiological processes such as energy and lipid metabolism. Here, we investigate how succinate, a TCA cycle intermediate that is a major predicted release product of gut bacteria in Drosophila, influences the nutritional physiology of its Drosophila host. We administered succinate as a dietary supplement to microbe- free Drosophila, and quantified key nutritional indices. Dietary succinate significantly reduced fly lipid levels by up to ∼50%. This response was not replicated in parallel experiments conducted with dietary fumarate supplement, indicating that it could not be attributed to a general effect of TCA intermediates. We hypothesize that microbe-derived succinate may contribute to the reduced lipid content of Drosophila bearing gut bacteria, relative to axenic Drosophila. More generally, this study high- lights the importance of microbial-derived metabolites as regulators of host metabolism.