What is the nature of a complex organism? Metagenomic research and its insights into biosystem function have fundamentally altered the answer to this question. High-throughput sequencing technology has revealed the multitude of microbes that live in and on human beings and other mammals. Metagenomics is beginning to uncover the relationships between microbiome and host that contribute to a complex organism's biological processes. The vast quantities of data generated by sequencing have also created analytical challenges that require new methods to identify biologically meaningful results. The research described in this dissertation applies many of these techniques to elucidate the role of microbiota in human health. Chapter 1 presents results from our study of human choline metabolism that identified a relationship between the human gut microbiome and health. Primer design and qPCR experiments that confirm Chapter 1 results are explained in Chapter 2. Chapter 3 characterizes the microbial community from cystic fibrosis lung infection exposed to repeated courses of antibiotic therapy. An experiment designed to improve the resolution of ARISA, a metagenomic profiling technique, is described in Chapter 4. In Chapter 5, the relationship between gut microbial community composition and exercise in mice is investigated. In total, the work in this dissertation identifies several novel relationships between microbiota, host and environmental factors that may prove important in identifying underlying biological mechanisms that will improve human health.