Phenolics-rich prebiotic fiber has been correlated with a number of positive health outcomes, however their bioavailability is typically low. A large portion the gut microbiota metabolize these fibers releasing a range of phenolic acids, which are believed to be principle bioactive components driving reduction in disease risk. Despite this, little evidence exists linking specific gut bacteria with the metabolites they produce and the downstream biological effects that these compounds exert. We therefore propose to assemble a cohort of individuals that will receive prebiotic supplementation, during comprehensive, longitudinal characterization of the microbiota and host changes with multiple omics assays (Aim 1). We will then integrate these multiomic data (Aim 2), generating unique biological signatures that define the role microbial metabolites from specific bacteria play in host biological activity. We will then isolate the microbial strains and metabolites associated with host biological activity, validate their function in gnotobiotic mice and synthesize the newly identified microbial molecules in vitro and demonstrate their structure, biological properties and applications (Aim 3). Through this study we expect to gain a detailed and clear understanding of the physiological changes, at the mechanistic level, that occur in the microbiome and host in response to dietary supplementation with prebiotic fiber.

Public Health Relevance

We propose a comprehensive, multiomic study that will integrate longitudinal data associating changes in specific gut bacteria and host in response to prebiotic fiber supplementation. These data will guide our development of an integrative biological signature relating bacterial-derived metabolites with biological outcome in the host. The open sharing of data generated by our proposed research represents a significant public resource that will support and accelerate future novel studies.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT010232-03
Application #
9994219
Study Section
Special Emphasis Panel (ZAT1)
Program Officer
Kim, Hye-Sook
Project Start
2018-09-20
Project End
2022-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305