Stochastic microbiome assembly depends on context

, interactions between bacteria can affect the microbiome assembly process, contributing to a baseline level of microbiome variability even among isogenic 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 at the same high concentration. We develop an ecological technique that infers the presence of interactions between bacterial species based on their colonization odds in different contexts, requiring only presence/absence data from two-species experiments. We use a progressive sequence of probabilistic models, in which the colonization of each bacterial species is treated as an independent stochastic process, to reproduce the empirical distributions of colonization outcomes across experiments. We find that incorporating context-dependent interactions substantially improves the performance of the models. Stochastic, context-dependent microbiome assembly underlies clinical therapies like fecal microbiota transplantation and probiotic administration and should inform the design of synthetic fecal transplants and dosing regimes.