Stochastic acquisition of the gut microbiome in Drosophila melanogaster

Observational studies reveal substantial variability in microbiome composition across individuals. While some of this variability can be explained by external factors like environmental, dietary, and genetic differences between individuals, here we show that the process of microbiome assembly is inherently stochastic for the model organism Drosophila melanogaster. Individuals are constantly exposed to microbial organisms that may or may not colonize their gut microbiome, and this contributes a baseline level of microbiome variability even among organisms that are identically reared, housed, and fed. In germ-free flies fed known combinations of bacterial species, we find that some species colonize more frequently than others even when fed identically. Incorporating context-dependent interactions substantially improves our ability to explain the observed variability in colonization outcomes. Stochastic, context-dependent microbiome assembly underlies clinical therapies like fecal microbiota transplantation and probiotic administration, and is relevant for the design of synthetic fecal transplants and dosing regimes.