The human gut microbiota: New analyses and methods on the continuum between disease and health

The human microbiota, commensal microbes that live in and on the human body, engender the Greek word commensal, “to eat at the same table.” The resident microbiota, as they eat food and waste products, interact in countless beneficial and neutral ways with humans. Even the historical focus on pathogenic strains has expanded to consider the potentially pathogenic function of a distorted community or loss of important members. This dissertation explores the field of human microbial ecology, host-microbe interactions, and methods used to characterize and analyze microbial communities. In the first data chapter I explore a microbial community in the distal human ileum whose populations have inverted following small bowel transplantation (SBT). I transition from this dramatic change in the ileum to a smaller magnitude of microbial population disruption associated with inflammatory bowel disease in the colon. The next two chapters focus on methods and the development of software tools that identify the taxonomy of 16S rDNA sequences and automate many of the bioinformatics tasks required to ecologically characterize a 16S rDNA survey of a microbial community. Using these tools as proof-of-principle on both the small bowel transplant and inflammatory bowel disease microbiota datasets (and other published datasets) inherently links the distinct fields of human gut microbial ecology and software development. The merging of bioinformatics and human microbiology enabled novel insights into these gut microbial communities, expanded and standardized these methods for the community, and broadened our understanding of the commensal microbiota’s role in human health