The investigators 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 the development of an integrative biological signature relating bacterial-derived metabolites with biological outcome in the host. The open sharing of data generated by the proposed research represents a significant public resource that will support and accelerate future novel studies.
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. With this study, the investigators propose to assemble a cohort of healthy individuals that will receive prebiotic supplementation, during comprehensive, longitudinal characterization of the microbiota and host changes with clinical markers and multiple omics assays. These multiomic data will then be integrated, generating unique biological signatures that define the role that microbial metabolites from specific bacteria play in host biological activity. To validate the biological function of these microbial metabolites, gnobiotic mice will be inoculated with the microbial strains identified. The newly identified metabolites will also be synthesized in vitro to demonstrate their structure, biological properties and applications. Through this study the investigators 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
100
Participants will complete 4 cycles. For each cycle they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Arabinoxylan. On cycle 2, they will take 20g per day of Beta-Glucan. On cycle 3, they will take 20g per day of Resistant Starch. On cycle 4, they will take 20g per day of Inulin.
Participants will complete 4 cycles. For each cycle they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Arabinoxylan. On cycle 2, they will take 20g per day of Beta-Glucan. On cycle 3, they will take 20g per day of Inulin. On cycle 4, they will take 20g per day of Resistant Starch.
Stanford University
Stanford, California, United States
Mapping of microbiota changes in response to prebiotic intervention
A detailed map of microbes and microbial gene expression changes during the intervention will be developed. Microbiota complexity in fecal samples will be determined by shotgun metagenomic sequencing. Novel microbes and gene pathways will be identified by de novo assemble of whole fecal metagenomes.
Time frame: 3 years
Comprehensive phenotyping of host profile during prebiotic intervention
Changes in host (human) phenotypic profile during the prebiotic intervention will be determined. Profile will include the metagenome, transcriptome, metabolome and cytokines of participants during the prebiotic intervention.
Time frame: 4 years
Biological signatures identified from the integration of microbiome-host omes
Biological signatures will be developed from the integration of the omics data with microbial metabolite levels.
Time frame: 4 years
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Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Arabinoxylan. On cycle 2, they will take 20g per day of Resistant Starch. On cycle 3, they will take 20g per day of Beta-Glucan. On cycle 4, they will take 20g per day of Inulin.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Arabinoxylan. On cycle 2, they will take 20g per day of Resistant Starch. On cycle 3, they will take 20g per day of Inulin. On cycle 4, they will take 20g per day of Beta-Glucan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Arabinoxylan. On cycle 2, they will take 20g per day of Inulin. On cycle 3, they will take 20g per day of Beta-Glucan. On cycle 4, they will take 20g per day of Resistant Starch.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Arabinoxylan. On cycle 2, they will take 20g per day of Inulin. On cycle 3, they will take 20g per day of Resistant Starch. On cycle 4, they will take 20g per day of Beta-Glucan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Beta-Glucan. On cycle 2, they will take 20g per day of Arabinoxylan. On cycle 3, they will take 20g per day of Resistant Starch. On cycle 4, they will take 20g per day of Inulin.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Beta-Glucan. On cycle 2, they will take 20g per day of Arabinoxylan. On cycle 3, they will take 20g per day of Inulin. On cycle 4, they will take 20g per day of Resistant Starch.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Beta-Glucan. On cycle 2, they will take 20g per day of Resistant Starch. On cycle 3, they will take 20g per day of Inulin. On cycle 4, they will take 20g per day of Arabinoxylan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Beta-Glucan. On cycle 2, they will take 20g per day of Resistant Starch. On cycle 3, they will take 20g per day of Arabinoxylan. On cycle 4, they will take 20g per day of Inulin.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Beta-Glucan. On cycle 2, they will take 20g per day of Inulin. On cycle 3, they will take 20g per day of Arabinoxylan. On cycle 4, they will take 20g per day of Resistant Starch.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Beta-Glucan. On cycle 2, they will take 20g per day of Inulin. On cycle 3, they will take 20g per day of Resistant Starch. On cycle 4, they will take 20g per day of Arabinoxylan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Resistant Starch. On cycle 2, they will take 20g per day of Inulin. On cycle 3, they will take 20g per day of Beta-Glucan. On cycle 4, they will take 20g per day of Arabinoxylan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Resistant Starch. On cycle 2, they will take 20g per day of Inulin. On cycle 3, they will take 20g per day of Arabinoxylan. On cycle 4, they will take 20g per day of Beta-Glucan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Resistant Starch. On cycle 2, they will take 20g per day of Arabinoxylan. On cycle 3, they will take 20g per day of Inulin. On cycle 4, they will take 20g per day of Beta-Glucan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Resistant Starch. On cycle 2, they will take 20g per day of Arabinoxylan. On cycle 3, they will take 20g per day of Beta-Glucan. On cycle 4, they will take 20g per day of Inulin.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Resistant Starch. On cycle 2, they will take 20g per day of Beta-Glucan. On cycle 3, they will take 20g per day of Inulin. On cycle 4, they will take 20g per day of Arabinoxylan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Resistant Starch. On cycle 2, they will take 20g per day of Beta-Glucan. On cycle 3, they will take 20g per day of Arabinoxylan. On cycle 4, they will take 20g per day of Inulin.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Inulin. On cycle 2, they will take 20g per day of Resistant Starch. On cycle 3, they will take 20g per day of Arabinoxylan. On cycle 4, they will take 20g per day of Beta-Glucan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Inulin. On cycle 2, they will take 20g per day of Resistant Starch. On cycle 3, they will take 20g per day of Beta-Glucan. On cycle 4, they will take 20g per day of Arabinoxylan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Inulin. On cycle 2, they will take 20g per day of Beta-Glucan. On cycle 3, they will take 20g per day of Resistant Starch. On cycle 4, they will take 20g per day of Arabinoxylan.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Inulin. On cycle 2, they will take 20g per day of Beta-Glucan. On cycle 3, they will take 20g per day of Arabinoxylan. On cycle 4, they will take 20g per day of Resistant Starch.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Inulin. On cycle 2, they will take 20g per day of Arabinoxylan. On cycle 3, they will take 20g per day of Beta-Glucan. On cycle 4, they will take 20g per day of Resistant Starch.
Participants will complete 4 cycles. For each cycle, they will take 20g per day fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks. On cycle 1, they will take 20g per day of Inulin. On cycle 2, they will take 20g per day of Arabinoxylan. On cycle 3, they will take 20g per day of Resistant Starch. On cycle 4, they will take 20g per day of Beta-Glucan.