Gut microbiome diversity is thought to be good for animal health. However, no solid body of evidence supports the generalities of that claim, and several recent papers have shown that germ free flies live longer than flies with their typical bacteria. Here we present evidence that intermediate levels of microbial diversity in the Drosophila melanogaster gut promote fly health even when a suitably nutritious diet is provided. We assembled a gnotobiotic fly colonized with all of the bacterial strains consistently found in our laboratory stock flies, of which there are two Lactobacilli and three Acetobacter for a total of five strains. We then measured fly development time with every possible combination of the defined bacterial strains for a total of 32 combinations. We find overall that flies colonized with any single bacterial strain are the slowest to develop, but that flies colonized by all strains are also slow to develop. On nutritionally poor diets, however, some bacteria speed up development while others are detrimental. In flies colonized with combinations of bacterial strains, benign strains can offset the effects of detrimental strains. In a limited set of gnotobiotic fly lifespan experiments, we see a similar overall trend whereby germ free flies and flies with intermediate levels of microbial diversity live the longest.
We used the gnotobiotic fly development time data to build a microbial epistatic interaction map (i.e. a food web) to determine how microbe-microbe interactions affect fly development, noting an abundance of weak interactions. Separate measurements of microbial interactions inside the fly gut indicate that detrimental bacterial strains can promote colonization by beneficial strains. These combinations are more beneficial to the fly, providing an ecological mechanism by which specific microbial interactions and not just absolute strain numbers account for the health phenotypes we observe. In vitro growth assays and bioinformatics suggest syntrophic exchange of nutrients, specifically lactic acid and B-vitamins, as the mechanisms for these microbial interactions inside the fly.
We propose that maintaining a diverse gut microbiome serves as a bet hedge against the more severe consequences of dominance by detrimental strains.