Determinants of microbial colonization and resilience in the human gut

Fecal microbiota transplantation (FMT), the process of transferring stool from a donor to a recipient's gastrointestinal tract, collides donor and recipient gut microbial communities chaotically in an already perturbed gut ecosystem. This provides ideal conditions to observe microbial colonization, succession, and competition in the human gut. In this dissertation, I use FMT as a model system in which to study the features of microbes that successfully colonize the human gut ecosystem. I employ genome-resolved metagenomics, high resolution metagenomic read-recruitment analyses, ecological theory, and publicly available data to interrogate the complex ecological and evolutionary events set in motion by FMT. I reveal the ecological forces driving microbial colonization after FMT, identify key metabolic pathways and functions associated with colonization and resilience in perturbed gut environments, and observe rapid genomic structural alterations to the same microbial populations within weeks of colonizing different hosts. Finally, I demonstrate the strength of the computational approaches used in this dissertation to evaluate, inform, and expand the context of bench lab studies through three interdisciplinary side projects. Ultimately, this dissertation bridges a gap between 'omics studies and hypothesis testing by providing targets for mechanistic studies in real world systems to untangle the forces driving microbial gut colonization.