Influence of the Gut Microbiome on Blueberry Polyphenol Metabolites (BlueBIOME)

The objective of this study is to determine whether inter-individual differences in the gut microbiome influence exposure to blueberry polyphenol metabolites. We will use pharmacokinetics of blueberry polyphenols after an acute blueberry exposure to group individuals into "metabotypes", groups of individuals based on similarity in their metabolite profiles. We will then use multi-omic approaches to determine whether the gut microbiome predicts an individual's metabotype.

Study Overview

• Status: Recruiting
• Conditions: Metabolomics; Microbiome Analysis
• Intervention / Treatment: Other: Freeze-dried blueberry powder beverage

Detailed Description

This study is an acute, single-arm polyphenol pharmacokinetic study designed to evaluate inter-individual variability in the metabolism of blueberry polyphenols and the role of the gut microbiome in shaping these responses. The study will be conducted at Colorado State University in the Food & Nutrition Clinical Research Laboratory. We will enroll approximately 125 healthy adults (≥18 years of age), with stratified recruitment across a range of ages and body mass index (BMI) values to capture diversity in gut microbiome composition. Participants will provide written informed consent prior to participation and will be compensated for their time.

Eligible participants will be generally healthy adults able to provide informed consent and adhere to study procedures. Key exclusion criteria include pregnancy or breastfeeding; pre-specified chronic diseases; recent antibiotic use; conditions affecting nutrient absorption; anemia; BMI ≤18.5 kg/m²; unwillingness to adhere to study protocols; recent blood draw within 1 week; participation in another research study; and contraindications to study procedures, treatments, or supplies.

The study consists of three main components: a screening visit, an acute test day, and a 24-hour follow-up visit. During the initial screening visit, participants will complete a health and medical history questionnaire, anthropometric assessments, blood pressure measurements, and a fasting blood draw to assess metabolic health and eligibility.

Following screening, participants will complete a short lead-in period prior to the test day, during which they will collect stool samples and a 24-hour urine sample at home and complete three 24-hour dietary recalls. They will also follow a low-polyphenol diet for three days prior to the test visit to minimize background variability in polyphenol exposure.

On the test day, participants will report to the laboratory following an overnight fast. Participants will consume a standardized blueberry beverage containing freeze-dried blueberry powder. Serial blood samples will be collected via an indwelling catheter at baseline and at multiple time points over an 8-hour period (0, 1, 2, 4, 6, and 8 hours) to characterize the pharmacokinetics of circulating blueberry polyphenol metabolites. Additional blood samples will be collected for peripheral blood mononuclear cell (PBMC) isolation at hours 4 and 6. Standardized low-polyphenol meals and snacks will be provided during the visit. Participants will also initiate a 24-hour urine collection and receive a stool collection kit for post-visit sampling.

Participants will return approximately 24 hours after blueberry consumption for a follow-up visit, which includes an additional fasting blood draw and return of urine and stool samples.

Throughout the study, additional data will be collected via validated questionnaires assessing gastrointestinal symptoms, sleep quality, physical activity, diet, and social determinants of health. Biological samples (blood, urine, and stool) will be used to assess polyphenol metabolism, gut microbiome composition and function, and related multi-omic profiles.

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tiffany Weir, PhD; Phone Number: (970) 491-4631; Email: tiffany.weir@colostate.edu
• Study Contact Backup: Name: Jenny Whittington, MS; Phone Number: (970) 310-6843; Email: ijwhitt@rams.colostate.edu

Study Locations

• United States
  • Colorado
    • Fort Collins, Colorado, United States, 80523
      • Recruiting
      • Colorado State University; Food and Nutrition Clinical Research Laboratory; Gifford Building Room 216; 502 West Lake Street, Fort Collins, CO 80523
      • Principal Investigator: Tiffany Weir, PhD
      • Contact: Jenny Whittington, MS; Phone Number: 970-310-6843; Email: ijwhitt@rams.colostate.edu
      • Contact: Tiffany Weir, PhD; Email: Tiffany.weir@colostate.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy adults ≥18 years of age
• Able and willing to provide informed consent
• Willing and able to adhere to all study procedures and visit requirements

Exclusion Criteria:

• Age <18 years
• Pregnant or breastfeeding
• Presence of chronic diseases, including but not limited to cardiovascular disease, diabetes, cancer, kidney, liver, gastrointestinal, or pancreatic disease
• Use of medications for chronic diseases that may interfere with study outcomes
• Any condition known to negatively impact nutrient absorption (e.g., inflammatory bowel disease, celiac disease, gastroparesis)
• Anemia (hemoglobin <13.5 g/dL in men or <12.0 g/dL in women)
• Body mass index (BMI) ≤18.5 kg/m²
• Use of antibiotics within the past 2 months
• Recent blood draw within 1 week prior to study participation
• Currently participating in another research study involving a diet or exercise intervention
• Known allergy or contraindication to blueberry products or study procedures
• Unwilling or unable to comply with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single-arm; All participants will receive a single dose of the blueberry intervention to characterize pharmacokinetic profiles of polyphenol metabolites.

Other: Freeze-dried blueberry powder beverage; Participants will consume a single oral dose of a standardized blueberry beverage prepared with 22 g of freeze-dried blueberry powder reconstituted in approximately 480 mL of distilled water. The beverage will be consumed in its entirety at the start of the test visit following an overnight fast. This dose is selected to provide a defined quantity of blueberry-derived polyphenols for pharmacokinetic assessment. No additional interventions or comparator treatments will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Area under the curve (AUC) of circulating blueberry polyphenol metabolites	Pharmacokinetics - Area under the curve (AUC) will be calculated from plasma concentrations of blueberry-derived polyphenol metabolites, measured at serial time points following a single-dose blueberry intervention.	Baseline and 1, 2, 4, 6, 8 and 24 hours post-consumption
Pharmacokinetics - Maximum concentration (Cmax) of circulating blueberry polyphenol metabolites	Pharmacokinetics - Maximum concentration (Cmax) will be calculated from plasma concentrations of blueberry-derived polyphenol metabolites, measured at serial time points following a single-dose blueberry intervention.	Baseline and 1, 2, 4, 6, 8 and 24 hours post-consumption
Pharmacokinetics - Time to maximum concentration (Tmax) of circulating blueberry polyphenol metabolites	Pharmacokinetics - Time to maximum concentration (Tmax) will be calculated from plasma concentrations of blueberry-derived polyphenol metabolites, measured at serial time points following a single-dose blueberry intervention.	Baseline and 1, 2, 4, 6, 8 and 24 hours post-consumption

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary excretion of blueberry polyphenol metabolites	Urinary concentrations of blueberry-derived polyphenol metabolites will be measured via 24-hour urine collection to assess excretion profiles following a single-dose blueberry intervention.	up to 24 hours post-consumption
Gut microbial taxonomic profiling	16s rRNA gene amplicon sequencing of stool samples will be used for exploratory gut microbial taxonomic profiling.	Baseline
Gut microbial functional potential	Metagenomic shotgun sequencing of stool samples will be used for exploratory profiling of gut microbial functional potential.	Baseline
Gut microbial transcripts	Metatranscriptomics will be used for exploratory profiling of gut microbial transcripts.	Baseline
Polyphenol Metabotype	Machine learning methods will be used to determine participant polyphenol metabotypes from pharmacokinetic profiles.	Baseline

Collaborators and Investigators

• Sponsor: Colorado State University
• Collaborators: King's College London; National Center for Complementary and Integrative Health (NCCIH); Florida State University; University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Microbiome; Pharmacokinetics; Metabolites; Polyphenols; Metabotype
• Other Study ID Numbers: 6959; 1RM1AT013318-01 (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