Environmentally mediated interactions predict community assembly and invasion success in a gut microbiota synthetic...

The gut microbiome plays a crucial role in host homeostasis, with implications for nutrition, immune development, metabolism, and protection against pathogens. Disturbance of the microbiome by microbial invasion can be negative or positive: invasions of opportunistic pathogens can cause disease while dysbiotic states need invasions to recover. However, the complexity of the microbiome challenges our understanding of what factors determine the ability of microbes to invade. In this study, we measure interactions between members of a synthetic community of prominent gut bacteria using supernatant assays, which quantify the growth of one species in the cell-free culture medium of another. We measure relative abundances of co-cultures of up to four species to validate a generalized Lotka-Volterra model parameterized with these supernatant assays. We predict differential invasion outcomes of the opportunistic pathogens Escherichia coli and Bacteroides ovatus based on their monoculture growth profiles and interactions with other species, and we experimentally confirm model predictions of invasion success. The predictive value of our model indicates that environmentally mediated interactions, e.g., through soluble chemicals, primarily determine co-culture abundances and invasion success. Furthermore, model analyses show that negative interactions within the resident community and neutral to positive interactions with the invading species promote invasion success, but the interactions toward the invading species dominate. Our validated approach opens the way for testing of interactions of human gut microbiome species, thereby developing interventions to avoid pathogenic overgrowth and therapies to enhance health-benefitting invasions.IMPORTANCEThe stability of the human gut microbiome is crucial for host health, with opportunistic pathogen invasions causing diseases and healthy strain replacements needed for recovery. The microbiota's complexity complicates the understanding of invasion outcomes. This study uses a 10-species synthetic community of common gut microbiota to predict stable communities and invasion success. We grow cells in the growth medium of other species with the cells removed to parameterize a computational model, accurately predicting community composition up to four species and invasion success of Escherichia coli and Bacteroides ovatus. Our findings show that interactions through soluble compounds in the environment dictate co-culture growth and invasions. Furthermore, model analysis shows that interactions within the resident community and toward the invader are both important, but the latter dominate. These results pave the way for larger-scale studies to characterize gut microbiome interactions and properties that resist invasions, potentially benefiting health through improved probiotics and fecal microbiota transplants.