Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components
- Conditions
- PreDiabetesDysbiosisEndotoxemiaInflammation
- Interventions
- Other: Whole Wheat BreadOther: White Bread (control)
- Registration Number
- NCT05318183
- Lead Sponsor
- Ohio State University
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 40
- Fasting blood glucose between 100-125 mg/dL
- BMI of 30-35 kg/m2
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Whole Wheat Bread Whole Wheat Bread Participants consuming 128 g of whole wheat bread (4 slices of bread) daily for two weeks White Bread (control) White Bread (control) Participants consuming 128 g of white bread (4 slices of bread) daily for two weeks
- Primary Outcome Measures
Name Time Method Change in fasting plasma glucose Day 0, Day 14 Fasting plasma glucose concentrations (mg/dL) will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
- Secondary Outcome Measures
Name Time Method Change in insulin sensitivity Day 14 Evaluated through an oral glucose tolerance test and quantified using the area under the curve (AUC) of the temporal changes in blood glucose and insulin conducted at the end of each intervention arm to assess between-treatment effects.
Level of myeloid differentiation factor 88 gene expression Day 0, Day 14 Expression of pro-inflammatory myeloid differentiation factor 88 gene from peripheral blood mononuclear cells will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Change in plasma insulin Day 0, Day 14 Plasma concentration (μIU/mL) of insulin will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Small gastrointestinal permeability Day 14 Lactulose/mannitol ratio will be measured in urine collected 0-5 h following the digestion of non-digestible sugar probes to assess small intestinal permeability. Excretion ratios will be measured at the end of each intervention arm to assess between-treatment effects.
Metabolic Endotoxemia Day 0, Day 14 Serum endotoxin concentration (EU/mL) will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Level of tumor necrosis factor alpha gene expression Day 0, Day 14 Expression of pro-inflammatory tumor necrosis factor alpha gene from peripheral blood mononuclear cells will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Level of interleukin-8 gene expression Day 0, Day 14 Expression of pro-inflammatory interleukin-8 gene from peripheral blood mononuclear cells will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Colonic gastrointestinal permeability Day 14 Sucralose/erythritol ratio will be measured in urine collected 6-24 h following digestion of non-digestible sugar probes to access colonic permeability. Excretion ratios will be measured at the end of each intervention arm to assess between-treatment effects.
Level of toll-like receptor 4 gene expression Day 0, Day 14 Expression of pro-inflammatory toll-like receptor 4 gene from peripheral blood mononuclear cells will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Serum myeloperoxidase Day 0, Day 14 Serum concentration (ng/mL) of myeloperoxidase will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Level of p65 subunit of nuclear factor kappa B gene expression Day 0, Day 14 Expression of pro-inflammatory p65 subunit of nuclear factor kappa B gene from peripheral blood mononuclear cells will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Level of interleukin-6 gene expression Day 0, Day 14 Expression of pro-inflammatory interleukin-6 gene from peripheral blood mononuclear cells will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Level of myeloperoxidase gene expression Day 0, Day 14 Expression of pro-inflammatory myeloperoxidase gene from peripheral blood mononuclear cells will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Fecal short-chain fatty acid: isovaleric acid Day 0, Day 14 Fecal concentrations (mmol/kg) of isovaleric acid will be measured in samples collected at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Level of monocyte chemoattractant protein-1 gene expression Day 0, Day 14 Expression of pro-inflammatory monocyte chemoattractant protein-1 gene from peripheral blood mononuclear cells will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Serum whole wheat bread phytochemical: phenolic compounds Day 0, Day 14 Serum concentrations of (nmol/L) phenolic compounds and phenolic derivatives will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Intestinal whole wheat phytochemical: benoxazinoids Day 0, Day 14 Fecal concentrations of (μmol/L) benoxazinoids and benoxazinoids derivatives will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Intestinal whole wheat phytochemical: phenolic compounds Day 0, Day 14 Fecal concentrations of (μmol/L) phenolic compounds and phenolic derivatives will be measured at the beginning and end of each intervention arm to assess within-treatment and between treatment effects.
Fecal calprotectin Day 0, Day 14 Fecal concentration (μg/g) of calprotectin will be measured in samples collected and the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Fecal myeloperoxidase Day 0, Day 14 Fecal concentration (ng/g) of myeloperoxidase will be measured in samples collected at the beginning and end of each study arm to assess within-treatment and between-treatment effects.
Fecal short-chain fatty acid: butyrate Day 0, Day 14 Fecal concentrations (mmol/kg) of butyrate will be measured in samples collected at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Fecal short-chain fatty acid: acetate Day 0, Day 14 Fecal concentrations (mmol/kg) of acetate will be measured in samples collected at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Fecal short-chain fatty acid: propionate Day 0, Day 14 Fecal concentrations (mmol/kg) of propionate will be measured individually in samples collected at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Fecal short-chain fatty acid: isobutyric acid Day 0, Day 14 Fecal concentrations (mmol/kg) of isobutyric acid will be measured in samples collected at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Serum whole wheat bread phytochemical: alkylersorcinols Day 0, Day 14 Serum concentrations of (nmol/L) alkylresorcinol and alkylresorcinol derivatives will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Serum whole wheat bread phytochemical: benoxazinods Day 0, Day 14 Serum concentrations of (nmol/L) benoxazinoids and benoxazinoids derivatives will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Intestinal whole wheat phytochemical: alkylresorcinols Day 0, Day 14 Fecal concentrations of (μmol/L) alkylresorcinols and alkylresorcinol derivatives will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.
Trial Locations
- Locations (1)
The Ohio State University
🇺🇸Columbus, Ohio, United States