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.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1OD000964-05
Application #
7924714
Study Section
Special Emphasis Panel (ZGM1-NDPA-G (P2))
Program Officer
Jones, Warren
Project Start
2006-09-28
Project End
2014-07-31
Budget Start
2010-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2010
Total Cost
$716,000
Indirect Cost
Name
Palo Alto Institute for Research & Edu, Inc.
Department
Type
DUNS #
624218814
City
Palo Alto
State
CA
Country
United States
Zip Code
94304
Proctor, Diana M; Fukuyama, Julia A; Loomer, Peter M et al. (2018) A spatial gradient of bacterial diversity in the human oral cavity shaped by salivary flow. Nat Commun 9:681
Proctor, Diana M; Relman, David A (2017) The Landscape Ecology and Microbiota of the Human Nose, Mouth, and Throat. Cell Host Microbe 21:421-432
Hoy, Yana Emmy; Bik, Elisabeth M; Lawley, Trevor D et al. (2015) Variation in Taxonomic Composition of the Fecal Microbiota in an Inbred Mouse Strain across Individuals and Time. PLoS One 10:e0142825
Relman, David A (2014) ""Inconvenient truths"" in the pursuit of scientific knowledge and public health. J Infect Dis 209:170-2
Yan, Miling; Pamp, Sünje J; Fukuyama, Julia et al. (2013) Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage. Cell Host Microbe 14:631-40
Debs, John E; Robins, Nicholas P; Close, John D (2013) Physics. Measuring mass in seconds. Science 339:532-3
Kashyap, Purna C; Marcobal, Angela; Ursell, Luke K et al. (2013) Genetically dictated change in host mucus carbohydrate landscape exerts a diet-dependent effect on the gut microbiota. Proc Natl Acad Sci U S A 110:17059-64
Sharon, Itai; Morowitz, Michael J; Thomas, Brian C et al. (2013) Time series community genomics analysis reveals rapid shifts in bacterial species, strains, and phage during infant gut colonization. Genome Res 23:111-20
Relman, David A (2013) Restoration of the gut microbial habitat as a disease therapy. Nat Biotechnol 31:35-7
Relman, David A (2013) Microbiology. Undernutrition--looking within for answers. Science 339:530-2

Showing the most recent 10 out of 31 publications