Multiomic Signatures of Microbial Metabolites Following Prebiotic Fiber Supplementation

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.

Study Overview

• Status: Recruiting
• Conditions: Prebiotics
• Intervention / Treatment: Dietary supplement: Fiber cycles

Detailed Description

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
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alessandra Celli, MS; Phone Number: (650) 725-8491; Email: alessandra.celli@stanford.edu
• Study Contact Backup: Name: Dalia Perelman, MS; Email: daliap@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94304
      • Recruiting
      • Stanford University
      • Contact: Dalia Perelman; Phone Number: 650-569-0462; Email: daliap@stanford.edu
      • Sub-Investigator: Dalia Perelman, MS, RD, CDE
      • Contact: Alessandra Celli; Phone Number: (650) 725-8491; Email: alessandra.celli@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- good general health

Exclusion Criteria:

• Chronic inflammatory conditions
• Major organ disease
• Heavy alcohol use
• Pregnancy/lactation
• Use of medication known to affect carbohydrate or lipid metabolism
• Active eating disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

24

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM 1: Arabinoxylan, Beta-Glucan, Resistant Starch, Inulin; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Arabinoxylan 2- Beta-Glucan 3- Resistant Starch 4- Inulin	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 2: Arabinoxylan, Beta-Glucan, Inulin, Resistant Starch; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Arabinoxylan 2- Beta-Glucan 3- Inulin 4- Resistant Starch	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 3: Arabinoxylan, Resistant Starch, Beta-Glucan, Inulin; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Arabinoxylan 2- Resistant Starch 3- Beta-Glucan 4- Inulin	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 4: Arabinoxylan, Resistant Starch, Inulin, Beta-Glucan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Arabinoxylan 2- Resistant Starch 3- Inulin 4- Beta-Glucan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 5: Arabinoxylan, Inulin, Beta-Glucan, Resistant Starch; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Arabinoxylan 2- Inulin 3- Beta-Glucan 4- Resistant Starch	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 6: Arabinoxylan, Inulin, Resistant Starch, Beta-Glucan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Arabinoxylan, 2- Inulin, 3- Resistant Starch, 4- Beta-Glucan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 7: Beta-Glucan, Arabinoxylan, Resistant Starch, Inulin; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Beta-Glucan, 2- Arabinoxylan, 3- Resistant Starch, 4- Inulin	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 8: Beta-Glucan, Arabinoxylan, Inulin, Resistant Starch; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Beta-Glucan, 2- Arabinoxylan, 3- Inulin, 4- Resistant Starch	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 9: Beta-Glucan, Resistant Starch, Inulin, Arabinoxylan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Beta-Glucan, 2- Resistant Starch, 3- Inulin, 4- Arabinoxylan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 10: Beta-Glucan, Resistant Starch, Arabinoxylan, Inulin; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Beta-Glucan, 2- Resistant Starch, 3- Arabinoxylan, 4- Inulin	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 11: Beta-Glucan, Inulin, Arabinoxylan, Resistant Starch; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Beta-Glucan, 2- Inulin, 3- Arabinoxylan, 4- Resistant Starch	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 12: Beta-Glucan, Inulin, Resistant Starch, Arabinoxylan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Beta-Glucan, 2- Inulin, 3- Resistant Starch, 4- Arabinoxylan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 13: Resistant Starch, Inulin, Beta-Glucan, Arabinoxylan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Resistant Starch 2- Inulin 3- Beta-Glucan 4- Arabinoxylan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 14: Resistant Starch, Inulin, Arabinoxylan, Beta-Glucan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Resistant Starch, 2- Inulin, 3- Arabinoxylan, 4- Beta-Glucan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 15: Resistant Starch, Arabinoxylan, Inulin, Beta-Glucan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Resistant Starch, 2- Arabinoxylan, 3- Inulin, 4- Beta-Glucan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 16: Resistant Starch, Arabinoxylan, Beta-Glucan, Inulin; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Resistant Starch, 2- Arabinoxylan, 3- Beta-Glucan, 4- Inulin	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 17: Resistant Starch, Beta-Glucan, Inulin, Arabinoxylan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Resistant Starch, 2- Beta-Glucan, 3- Inulin, 4- Arabinoxylan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 18: Resistant Starch, Beta-Glucan, Arabinoxylan, Inulin; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Resistant Starch, 2- Beta-Glucan, 3- Arabinoxylan, 4- Inulin	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 19: Inulin, Resistant Starch, Arabinoxylan, Beta-Glucan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Inulin, 2- Resistant Starch, 3- Arabinoxylan, 4- Beta-Glucan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 20: Inulin, Resistant Starch, Beta-Glucan, Arabinoxylan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Inulin, 2- Resistant Starch, 3- Beta-Glucan, 4- Arabinoxylan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 21: Inulin, Beta-Glucan, Resistant Starch, Arabinoxylan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Inulin, 2- Beta-Glucan, 3- Resistant Starch, 4- Arabinoxylan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 22: Inulin, Beta-Glucan, Arabinoxylan, Resistant Starch; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Inulin, 2- Beta-Glucan, 3- Arabinoxylan, 4- Resistant Starch	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 23: Inulin, Arabinoxylan, Beta-Glucan, Resistant Starch; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Inulin, 2- Arabinoxylan, 3- Beta-Glucan, 4- Resistant Starch	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.
Experimental: ARM 24: Inulin, Arabinoxylan, Resistant Starch, Beta-Glucan; Participants randomized in this arm will take the 4 fiber supplements in the following order: 1- Inulin, 2- Arabinoxylan, 3- Resistant Starch, 4- Beta-Glucan	Dietary supplement: Fiber cycles; Participants will take 20g per day of each fiber supplement for 3 weeks, followed by a washout period of at least 6-8 weeks before starting the next fiber supplement.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Michael P Snyder, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2020
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 16, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 23602; 5R01AT010232 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No