Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components

This study will investigate the gut microbiota-mediated effects of whole wheat consumption on human health in adults with pre-diabetes. Participants will complete two phases of intervention in random order in which they will consume either whole wheat bread (4 servings) or white bread a day for two weeks prior to collecting specimens (stool, urine, and plasma/serum).

Study Overview

• Status: Active, not recruiting
• Conditions: Inflammation; PreDiabetes; Endotoxemia; Dysbiosis
• Intervention / Treatment: Other: Whole Wheat Bread; Other: White Bread (control)

Detailed Description

Accumulating clinical evidence suggests positive effects of whole grain on cardiometabolic risk. However, outcomes of controlled trials indicate that substantial interpersonal variation occurs in these studies with regard to glucose homeostasis, with some persons being unaffected and others experiencing glucose-lowering effects due to whole wheat bread consumption. Whole grain (whole wheat) contains bioactive phytochemicals in addition to its well-recognized fiber content, and these constituents have not received adequate study to inform dietary recommendations. The objective of this study is to investigate the glucose-lowering effects of whole wheat bread in persons with prediabetes using multi-omics platforms that can provide an understanding of the complex interactions among the gut microbiome, gut metabolome, host metabolome, and gut barrier function. The hypothesis is that gut microbial metabolism of whole wheat and its major bioactive components is a determining factor of human health benefits. This will be tested by conducting a randomized, controlled crossover trial in persons with pre-diabetes who follow a controlled diet containing whole wheat bread or white bread for 2-weeks. Outcomes are expected to significantly advance an understanding of personalized, gut microbiome-mediated approaches in individuals with pre-diabetes to help guide dietary recommendations of whole wheat intake. In addition, novel evidence that maps out the differential functions of diverse genus/species of microbiota to biotransform whole wheat nutrients into more bioactive metabolites are expected.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Fasting blood glucose between 100-125 mg/dL
• BMI of 30-35 kg/m2

Exclusion Criteria:

• History of liver disease, cardiovascular disease, overt diabetes, or cancer
• Prescribed medications for hyperglycemia or dyslipidemia
• Use of dietary supplements, prebiotics, or probiotics
• Usage of antibiotics or anti-fungals within 3 months prior to enrollment
• Smoker
• Alcohol consumption greater than 2 drinks per day
• Aerobic exercise greater than 5 hours per week
• Pregnancy or fertility treatments
• History of chronically active inflammatory or neoplastic disease in 3 years prior to enrollment
• History of chronic gastrointestinal disorder including diarrhea, inflammatory bowel disease, celiac disease; coagulation disorders, chronic immunosuppressive medication usage
• History of myocardial infarction or cerebrovascular accident within 6 months prior to participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Whole Wheat Bread; Participants consuming 128 g of whole wheat bread (4 slices of bread) daily for two weeks	Other: Whole Wheat Bread; Standardized whole wheat bread (128 g daily)
Placebo Comparator: White Bread (control); Participants consuming 128 g of white bread (4 slices of bread) daily for two weeks	Other: White Bread (control); Standardized white bread (128 g daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glucose	Data are biomarker area under the time-concentration curve (0-3 hours) on day 14	Day 14 (0, 30, 60, 90, 120, 150, 180 minutes post oral glucose tolerance test)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Insulin	Data are biomarker fasting concentrations	Day 14
Plasma Glucose	Data are biomarker fasting concentrations.	Day 14
Serum C-reactive Protein	Data are the biomarker serum concentration of C-reactive protein.	Day 14
Serum Tumor Necrosis Factor Alpha	Data are biomarker serum tumor necrosis factor alpha concentrations.	Day 14
Serum Interleukin-6	Data are biomarker serum interleukin-6 concentrations.	Day 14
Fecal Calprotectin	Data are biomarker fecal concentrations.	Day 14
Fecal Myeloperoxidase	Data are biomarker fecal concentrations.	Day 14
Urine Lactulose/Mannitol	Data are the 24-hour urinary excretion ratio of lactulose relative to mannitol collected 0-5 h following the digestion of non-digestible sugar probes.	Day 14
Urine Sucralose/Erythritol	Data are the sucralose/erythritol ratio measured in urine collected 6-24 h following the digestion of non-digestible sugar probes.	Day 14
Serum Endotoxin	Data are biomarker fasting concentrations.	Day 14
Serum Myeloperoxidase	Data are biomarker serum concentrations.	Day 14
Level of Toll-like Receptor 4 Gene Expression	Data are expression of toll-like receptor 4 gene from peripheral blood mononuclear cells.	Day 14
Myeloid Differentiation Factor 88 Gene Expression	Expression of myeloid differentiation factor 88 gene from peripheral blood mononuclear cells.	Day 14
Tumor Necrosis Factor Alpha Gene Expression	Expression of tumor necrosis factor alpha gene from peripheral blood mononuclear cells.	Day 14
p65 Subunit of Nuclear Factor Kappa B Gene Expression	Expression of p65 subunit of nuclear factor kappa B gene from peripheral blood mononuclear cells.	Day 14
Interleukin-6 Gene Expression	Expression of interleukin-6 gene from peripheral blood mononuclear cells.	Day 14
Interleukin-8 Gene Expression	Expression of interleukin-8 gene from peripheral blood mononuclear cells.	Day 14
Myeloperoxidase Gene Expression	Expression of myeloperoxidase gene from peripheral blood mononuclear cells.	Day 14
Monocyte Chemoattractant Protein-1 Gene Expression	Expression of monocyte chemoattractant protein-1 gene from peripheral blood mononuclear cells.	Day 14
Fecal Butyrate	Data are biomarker fecal concentrations.	Day 14
Fecal Acetate	Data are biomarker fecal concentrations.	Day 14
Fecal Propionate	Data are biomarker fecal concentrations.	Day 14
Fecal Isobutyric Acid	Data are biomarker fecal concentrations.	Day 14
Fecal Isovaleric Acid	Data are biomarker fecal concentrations of isovaleric acid.	Day 14
Serum Alkylersorcinols	Data are biomarker serum concentrations of alkylresorcinol and alkylresorcinol derivatives.	Day 14
Serum Benoxazinods	Data are biomarker serum concentrations of benoxazinoids and benoxazinoids derivatives.	Day 14
Serum Phenolic Compounds	Data are biomarker serum concentrations of phenolic compounds and phenolic derivatives.	Day 14
Fecal Alkylresorcinols	Data are biomarker fecal concentrations of alkylresorcinols and alkylresorcinol derivatives.	Day 14
Fecal Benoxazinoids	Data are biomarker fecal concentrations of benoxazinoids and benoxazinoids derivatives.	Day 14
Fecal Phenolic Compounds	Data are fecal concentrations of phenolic compounds and phenolic derivatives.	Day 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Triglyceride	Data are biomarker fasting plasma concentrations.	Day 0, Day 14
Plasma Cholesterol Levels	Data are biomarker fasting plasma concentrations.	Day 14
Plasma HDL-cholesterol	Data are biomarker fasting plasma concentrations.	Day 14
Serum Alanine Transaminase	Data are biomarker serum concentrations of alanine transaminase.	Day 14
Serum Interleukin-8	Data are biomarker serum interleukin-8 concentrations.	Day 14
Gut Microbiota Alpha-diversity Indices	Alpha-diversity will be determined based on the Shannon-Wiener diversity index. Fecal microbiota assessments and the subsequent determinations of alpha-diversity.	Day 14
Gut Microbiota Beta-diversity Indices	Beta-diversity will be determined based on the Bray-Curtis diversity index. Fecal microbiota assessments and the subsequent determinations of beta-diversity.	Day 14
Gut Microbiota Relative Abundance	Gut microbiota relative abundance (percent order, genus, and species level) will be measured in fecal samples.	Day 14

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: United States Department of Agriculture (USDA)
• Investigators: Principal Investigator: Richard Bruno, PhD, RD, Ohio State University

Publications and helpful links

General Publications

• Cao S, Pierson JT, Bond AH, Zhang S, Gold A, Zhang H, Zamary KM, Moats P, Teegarden MD, Peterson DG, Mo X, Zhu J, Bruno RS. Intestinal-level anti-inflammatory bioactivities of whole wheat: Rationale, design, and methods of a randomized, controlled, crossover dietary trial in adults with prediabetes. Nutr Res. 2024 Nov;131:83-95. doi: 10.1016/j.nutres.2024.09.010. Epub 2024 Sep 18.

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Actual): May 30, 2024
• Study Completion (Estimated): May 30, 2026

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 8, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Microbiome; Prediabetes; Metabolomics; Gut microbiota; Intestinal permeability; Glycemic response; Gut dysbiosis; Microbiome metabolism; Whole Wheat; Phytochemicals
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Metabolic Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Glucose Metabolism Disorders; Diabetes Mellitus; Bacteremia; Toxemia; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Inflammation; Dysbiosis; Prediabetic State; Endotoxemia
• Other Study ID Numbers: 2021H0347

Drug and device information, study documents

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