In our effort to understand human biology and human individuality we emphasize the importance of our genetic blueprint, i.e., the human genome, and our environment. However, our view of self tends to ignore our microbial inhabitants, which outnumber our own cells by ten-fold. A growing body of evidence implicates these microbial inhabitants in a wide array of activities critical to human well-being, as well as to disease. Early molecular explorations of diversity within the human indigenous microbiota demonstrate vast populations of uncultivated and uncharacterized organisms, previously-unrecognized potential function, and significant variation between different human hosts. It is time to embrace a more extended view of self, one that emphasizes our mutualistic and symbiotic relationships with our microbiota, and one that considers the net human-microbe ?metagenome?. The first phase of the proposed work will entail a detailed molecular survey of the human indigenous microbiota. The second phase will examine variability in patterns of microbial diversity, as a function of human individuality (including genetics), age and time (microbial succession), space (biogeography within the host landscape), and human diet. A third phase will focus on the effects of perturbation, e.g. antibiotics, on the structure of human indigenous microbial communities (community robustness), as well as on the relationships between patterns of microbial diversity and mucosal health and disease. These efforts will have profound and practical implications for human biology and for the promotion of health. The goals of this work are a more complete understanding and definition of human health based on indigenous microbial community profiles, the identification of microbial community ?signatures? that predict the development or course of local disease, and strategies for the maintenance or restoration of health that involve well-informed manipulations of the human microbiota.
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