NIH Director's Pioneer Award

Stanford University, Stanford CA

Investigators

Linked publications & trials

Abstract

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