Gut Microbiomes
Conditions
Keywords
California Table Grapes, Third generation sequencing, anti-inflammation
Brief summary
This is a bio-specimen analysis and dietary intervention study that will examine whether the daily consumption of California table grape powder significantly modulates the gut microbiome and systemic immune profiles in healthy adults. The primary objective is to characterize longitudinal changes in microbial strains, metabolites, and immune markers following a 4-week grape intervention compared to a placebo. Methods include a screening of up to 300 individuals to evaluate pre-specified microbiome eligibility criteria, followed by a randomized, double-blind, placebo-controlled, parallel-group design where up to 40 participants will provide fecal and blood samples for high-resolution metagenomic sequencing and LC-MS/MS metabolomics at baseline, mid-study, and post-washout. Participants who meet the microbiome screening and other study eligibility criteria may be invited to participate in the intervention phase; participation in the screening phase does not guarantee enrollment in the intervention phase.
Detailed description
The human gut microbiome consists of trillions of microorganisms that are essential to host metabolism, immune system regulation, and the maintenance of disease resistance. Recent findings indicate that dietary changes can rapidly and significantly alter the composition of these microbial communities, leading to substantial effects on the host's overall physiology. Foods rich in polyphenols are highly effective at modulating this environment because they possess selective antimicrobial properties and exert beneficial prebiotic effects on the resident microbiota. Polyphenol-rich foods beneficially modulate the human gut microbiome with downstream metabolic and immune effects. California table grapes contain a complex mixture of phenolics, resveratrol, flavans, flavonols, and anthocyanins, making them ideal candidates for investigating gastrointestinal and immune health. However, previous grape-microbiome studies have been limited by small sample sizes (n=21-29), short durations (2 weeks), low-resolution microbiome technologies (16S profiling), and failure to measure corresponding inflammatory or immune biomarkers. This project will first conduct a microbiome screening phase in up to 300 healthy adults to identify individuals who meet pre-specified microbiome and other study eligibility criteria. Eligible individuals may then be invited to participate in a rigorous, multi-omic pilot study using standardized freeze-dried grape powder to determine how daily grape consumption modulates the gut microbiome-immune axis in up to 40 healthy adults. The study team will employ state-of-the-art metagenomic sequencing to achieve high-resolution microbiome profiling; metabolomic analysis; and immune biomarker profiling to assess gastrointestinal inflammation. Specific Aims Overarching Goal: To build on our unique expertise in high-resolution microbiome analyses to conduct a rigorous, multi-omic pilot study determining how daily consumption of California table grape powder modulates the human gut microbiome-immune axis in healthy adults. Hypothesis: Compared to a placebo, daily consumption of California table grape powder will beneficially modulate the gut microbiome by: (1) altering microbial composition; (2) shifting the fecal metabolome to increase grape-derived and microbial-derived anti-inflammatory compounds; and (3) reducing baseline biomarkers of gastrointestinal inflammation.
Interventions
DIETARY_SUPPLEMENTGrape Powder
72 g of grape powder for daily consumption for 28 days.
OTHERPlacebo Powder
72 g of matching placebo for daily consumption for 28 days.
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Random assignment to group; each individual will be identified by a number rather than any identifying info.
Intervention model description
Screen volunteers from fecal samples; select 40 and randomly assign 20 to grape powder intake, 20 to placebo powder intake. Collect fecal samples, screen for health markers.
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults between the ages of 45 and 65 years old * Body Mass Index (BMI) within the range of 18.5 to 25.9 kg/m² * Willing and able to provide informed consent * Agreement to maintain usual dietary patterns throughout the study, except for the provided study powder * Agreement to avoid
Exclusion criteria
(below) during the study period * Able and willing to collect and mail a stool sample during the microbiome screening phase and, if enrolled in the intervention phase, and at the three defined study timepoints * For enrollment into the intervention phase, meeting pre-specified microbiome eligibility criteria based on the screening stool sample, as defined in the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long read sequencing | 3 collections at T0 (after 3 weeks of dietary control), at week 4 (after grape or placebo powder daily), and at week 8 (after 4 weeks of returning back to normal diet) | Sequencing DNA from fecal samples to identify bacteria. This will assess whether the grape powder induces a change in the abundance of beneficial species/decrease in harmful species, following treatment, compared to control. This will be quantitatively assessed via sequencing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal metabolites profile from LC-MS/MS | 3 collections at T0 (after 3 weeks of dietary control), at week 4 (after grape or placebo powder daily), and at week 8 (after 4 weeks of returning back to normal diet) | Fecal metabolites as measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) |
| Fecal calprotectin level measured by ELISA | 3 collections at T0 (after 3 weeks of dietary control), at week 4 (after grape or placebo powder daily), and at week 8 (after 4 weeks of returning back to normal diet) | Fecal calprotectin as measured by ELISA. Elevated levels of calprotectin are a sensitive indicator of mucosal irritation. |
| Fecal albumin level measured by ELISA | 3 collections at T0 (after 3 weeks of dietary control), at week 4 (after grape or placebo powder daily), and at week 8 (after 4 weeks of returning back to normal diet) | Fecal albumin as measured by ELISA. Fecal albumin serves as a proxy for intestinal permeability, as its presence in the gut lumen suggests a leak across the epithelial barrier. |
| Fecal Lipocalin-2 measured by ELISA | 3 collections at T0 (after 3 weeks of dietary control), at week 4 (after grape or placebo powder daily), and at week 8 (after 4 weeks of returning back to normal diet) | Fecal Lipocalin-2 as measured by ELISA. Fecal Lipocalin-2 is produced by both epithelial and immune cells in response to bacterial stressors. |
Countries
United States
Contacts
CONTACTGang Fang, PhD
CONTACTEdward A Mead, PhD
PRINCIPAL_INVESTIGATORGang Fang, PhD
Icahn School of Medicine at Mount Sinai
Outcome results
None listed