Multiomic Signatures of Microbial Metabolites Following Prebiotic Fiber Supplementation

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Multiomic Signatures of Microbial Metabolites Following Prebiotic Fiber Supplementation

Conditions
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Prebiotics

Intervention / Treatment
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* Dietary Supplement: Fiber supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - good general health Exclusion Criteria: Fasting Blood Sugar >126 mg/dL Triglycerides >400 mg/dL Uncontrolled hypertension Vascular disease Chronic inflammatory conditions Major organ disease Heavy alcohol use Pregnancy/lactation Prior bariatric surgery Active psychiatric disease Use of medication known to affect carbohydrate or lipid metabolism Active eating disorder

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Interventional Model Description: Participants will be randomized to the order of the fiber supplementation and they will take each fiber for three weeks. After a washout period, they will switch fibers. Blood and stool samples will be collected through the intervention and once during each washout period.
Masking: Single


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: Fiber supplement|3 week sequential supplementation with each fiber supplement|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 4 years |