Household transmission of the human gut microbiota after antibiotic exposure

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PROJECT SUMMARY/ABSTRACT Humans constantly encounter microbes in their diets and environments, but only a tiny fraction of these microbes take up long-term residence in the adult gut microbiome. Microbiome therapeutics like probiotics and fecal microbiota transplants often seek to introduce new, desirable microbes, but these strains are frequently lost and fail to stably colonize existing communities. Understanding the ecological interactions that affect colonization and transmission is crucial for designing successful targeted microbiome therapeutics. Ecological theory predicts that factors like cross-feeding, nutrient competition, and priority effects may affect the ability of new microbes to colonize established communities, but there remain few examples of ecological interactions that affect colonization in the human gut microbiome. Here, we propose to investigate ecological interactions in microbial communities that affect colonization and transmission in natural and experimental gut microbial communities. We plan to focus on households, which are natural settings of microbial transmission. We have already recruited a longitudinal household cohort to document transmission after antibiotic exposure in the adult gut microbiome which allows us to determine how disturbances affect strain colonization. We will also use a novel experimental system to test the role of ecological factors like community diversity, ecological drift, and environmental perturbations. First, we will track transmission events within households in the human gut microbiome after antibiotic exposure by performing metagenomic sequencing of stool samples from the household cohort. By analyzing these data, we will identify transmission events that occur before and after antibiotic exposure, and we will track the trajectories of mutations that arise after strain transmission, as strains propagate in new hosts and communities. Next, we will characterize the effects of ecological drift and community diversity on transmission in ex vivo microbial communities. We have generated ex vivo communities from stool samples collected from our household cohort, and we will mix pairs of communities to evaluate the effects of strain dosage and community diversity on transmission. Finally, we will systematically mix ex vivo communities to identify strains capable of colonizing communities before and after antibiotic perturbation. Together, this work will provide important new information about the ecological factors that shape microbial colonization and transmission. The initial, exploratory work proposed here will also pave the way for future work that uses these collections of gut-derived communities to identify and characterize molecular and metabolic interactions between strains that affect microbial colonization, helping us design more effective, targeted microbiome therapeutics.