The complex relationship between humans and their microbiome and the changes of the microbiome during onset of human disease are poorly understood. We propose to form a multiomics Center for the detailed longitudinal analysis of both the microbiome, its activity, and its interconnected relationship with the host during healthy and disease states by omics profiling. Building upon our broad expertise, we will analyze several human microbiomes (fecal, nasal, and exogenous viral) in conjunction with host blood and urine components. Samples will be collected and analyzed during healthy and viral infections from the same individuals over the course of at least three years. Through analysis ofthe microbiome and host biological activities as measured through a variety of omics approaches (metagenome, genome, transcriptome, proteome, metabolome), we will follow the dynamic changes in the microbiome and host pathways that occur during viral infections and other potential stresses, and obtain an unprecedented view ofthe molecular pathways that change during this period. We will focus on subjects at risk for diabetes, and we will correlate the molecular changes in microbiome (endogenous and viral) activity with changes in host glucose levels and diabetes onset. Overall, more than 1080 different physiological states will be analyzed in omic detail and the microbiome and corresponding host information will be deposited in a public repository and serve as an invaluable resource to the scientific community. To accomplish this goal we have assembled a uniquely qualified team.

Public Health Relevance

Both viral and endogenous microbiomes are thought to have an enormous influence on human health but exactly how this occurs is not known. By analyzing in detail the gut and nasal microbiome and how its activity changes during viral infection in people we hope to understand in detail its influence on human physiology, particularly those at risk for diabetes. This information may help in understand how diabetes is acquired and ultimately may be useful for disease detection and treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54DE023789-01
Application #
8617384
Study Section
Special Emphasis Panel (ZDE1-JH (15))
Program Officer
Lunsford, Dwayne
Project Start
2013-09-06
Project End
2016-08-31
Budget Start
2013-09-06
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$2,499,572
Indirect Cost
$741,334
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Petersen, Lauren M; Bautista, Eddy J; Nguyen, Hoan et al. (2017) Community characteristics of the gut microbiomes of competitive cyclists. Microbiome 5:98
Misra, Ravi; Arebi, Naila (2017) Re: Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease. Gastroenterology 152:2082-2083
Yu, Kun-Hsing; Hart, Steven N; Goldfeder, Rachel et al. (2017) HARNESSING BIG DATA FOR PRECISION MEDICINE: INFRASTRUCTURES AND APPLICATIONS. Pac Symp Biocomput 22:635-639
Huang, Hailiang; Fang, Ming; Jostins, Luke et al. (2017) Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature 547:173-178
Kopylov, Uri; Boucher, Gabrielle; Waterman, Matti et al. (2016) Genetic Predictors of Benign Course of Ulcerative Colitis-A North American Inflammatory Bowel Disease Genetics Consortium Study. Inflamm Bowel Dis 22:2311-6
Blaser, Martin J; Cardon, Zoe G; Cho, Mildred K et al. (2016) Toward a Predictive Understanding of Earth's Microbiomes to Address 21st Century Challenges. MBio 7:
Rivas, Manuel A; Graham, Daniel; Sulem, Patrick et al. (2016) A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis. Nat Commun 7:12342
Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke et al. (2016) Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study. Lancet 387:156-67
Volkmann, Elizabeth R; Chang, Yu-Ling; Barroso, Nashla et al. (2016) Association of Systemic Sclerosis With a Unique Colonic Microbial Consortium. Arthritis Rheumatol 68:1483-92
Chu, Hiutung; Khosravi, Arya; Kusumawardhani, Indah P et al. (2016) Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science 352:1116-20

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