PT  - JOURNAL ARTICLE
AU  - Eric W. Jones
AU  - Jean M. Carlson
AU  - David A. Sivak
AU  - William B. Ludington
TI  - Stochastic microbiome assembly depends on context
AID  - 10.1101/2021.08.29.458111
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.29.458111
4099  - http://biorxiv.org/content/early/2021/08/29/2021.08.29.458111.short
4100  - http://biorxiv.org/content/early/2021/08/29/2021.08.29.458111.full
AB  - 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, in this paper we show that for the model organism Drosophila melanogaster the process of microbiome assembly is inherently stochastic and 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 at the same high concentration. We develop a new 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.Significance Statement Individuals are constantly exposed to microbial organisms that may or may not colonize their gut microbiome, and newborn individuals assemble their microbiomes through a number of these acquisition events. Since microbiome composition has been shown to influence host physiology, a mechanistic understanding of community assembly has potentially therapeutic applications. In this paper we study microbiome acquisition in a highly-controlled setting using germ-free fruit flies inoculated with specific bacterial species at known abundances. Our approach revealed that acquisition events are stochastic, and the colonization odds of different species in different contexts encode ecological information about interactions. These findings have consequences for microbiome-based therapies like fecal microbiota transplantation that attempt to modify a person’s gut microbiome by deliberately introducing foreign microbes.Competing Interest StatementThe authors have declared no competing interest.