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

Inflammation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05318183
• Other study ID #: 2021H0347
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 27, 2022
• Est. completion date: December 2025

Study information

• Verified date: January 2024
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Dysbiosis
• Endotoxemia
• Glucose Intolerance
• Inflammation
• PreDiabetes
• Prediabetic State

Intervention

Other:
• Whole Wheat Bread
Standardized whole wheat bread (128 g daily)
• White Bread (control)
Standardized white bread (128 g daily)

Locations

Country	Name	City	State
United States	The Ohio State University	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Ohio State University	USDA Beltsville Human Nutrition Research Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma triglyceride levels	Plasma triglyceride concentrations (mg/dL) will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.	Day 0, Day 14
Other	Plasma cholesterol levels	Plasma cholesterol concentrations (mg/dL) will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.	Day 0, Day 14
Other	Plasma HDL-cholesterol levels	Plasma HDL-cholesterol concentrations (mg/dL) will be measured at the beginning and end of each intervention arm to assess within-treatment and between-treatment effects.	Day 0, Day 14
Other	Serum alanine transaminase	Serum concentrations (U/L) of alanine transaminase will be measured at the beginning and end of each intervention arm to assess within-treatment and between treatment effects.	Day 0, Day 14
Other	Serum inflammatory biomarker: C-reactive protein	Serum concentration (mg/L) of C-reactive protein will be measured at the end of each intervention arm to assess between-treatment effects.	Day 14
Other	Serum inflammatory biomarker: interleukin-6	Serum interleukin-6 concentrations (pg/mL) of interleukin-6 will be measured at the end of each intervention arm to assess between-treatment effects.	Day 14
Other	Serum inflammatory biomarker: interleukin-8	Serum interleukin-8 concentrations (pg/mL) will be measured at the end of each intervention arm to assess between-treatment effects.	Day 14
Other	Serum inflammatory biomarker: tumor necrosis factor alpha	Serum tumor necrosis factor alpha concentrations (pg/mL) will be measured at the end of each intervention arm to assess between-treatment effects.	Day 14
Other	Gut microbiota alpha-diversity indices	Within-treatment and between-treatment effects regarding alpha-diversity will be determined based on the Shannon-Wiener diversity index. Fecal samples collected at the beginning and end of each intervention period will be used to perform microbiota assessments and the subsequent determinations of alpha-diversity.	Day 0, Day 14
Other	Gut microbiota beta-diversity indices	Within-treatment and between-treatment effects regarding beta-diversity will be determined based on the Bray-Curtis diversity index. Fecal samples collected at the beginning and end of each intervention period will be used to perform microbiota assessments and the subsequent determinations of beta-diversity.	Day 0, Day 14
Other	Gut microbiota relative abundance	Gut microbiota relative abundance (percent order, genus, and species level) will be measured in fecal samples collected at the beginning and end of each intervention arm to assess within-treatment and between treatment effects.	Day 0, Day 14
Primary	Change in fasting plasma glucose	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.	Day 0, Day 14
Secondary	Change in plasma insulin	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.	Day 0, Day 14
Secondary	Change in insulin sensitivity	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.	Day 14
Secondary	Small gastrointestinal permeability	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.	Day 14
Secondary	Colonic gastrointestinal permeability	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.	Day 14
Secondary	Metabolic Endotoxemia	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.	Day 0, Day 14
Secondary	Serum myeloperoxidase	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.	Day 0, Day 14
Secondary	Level of toll-like receptor 4 gene expression	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.	Day 0, Day 14
Secondary	Level of myeloid differentiation factor 88 gene expression	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.	Day 0, Day 14
Secondary	Level of tumor necrosis factor alpha gene expression	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.	Day 0, Day 14
Secondary	Level of p65 subunit of nuclear factor kappa B gene expression	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.	Day 0, Day 14
Secondary	Level of interleukin-6 gene expression	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.	Day 0, Day 14
Secondary	Level of interleukin-8 gene expression	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.	Day 0, Day 14
Secondary	Level of myeloperoxidase gene expression	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.	Day 0, Day 14
Secondary	Level of monocyte chemoattractant protein-1 gene expression	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.	Day 0, Day 14
Secondary	Fecal calprotectin	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.	Day 0, Day 14
Secondary	Fecal myeloperoxidase	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.	Day 0, Day 14
Secondary	Fecal short-chain fatty acid: butyrate	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.	Day 0, Day 14
Secondary	Fecal short-chain fatty acid: acetate	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.	Day 0, Day 14
Secondary	Fecal short-chain fatty acid: propionate	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.	Day 0, Day 14
Secondary	Fecal short-chain fatty acid: isobutyric acid	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.	Day 0, Day 14
Secondary	Fecal short-chain fatty acid: isovaleric acid	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.	Day 0, Day 14
Secondary	Serum whole wheat bread phytochemical: alkylersorcinols	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.	Day 0, Day 14
Secondary	Serum whole wheat bread phytochemical: benoxazinods	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.	Day 0, Day 14
Secondary	Serum whole wheat bread phytochemical: phenolic compounds	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.	Day 0, Day 14
Secondary	Intestinal whole wheat phytochemical: alkylresorcinols	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.	Day 0, Day 14
Secondary	Intestinal whole wheat phytochemical: benoxazinoids	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.	Day 0, Day 14
Secondary	Intestinal whole wheat phytochemical: phenolic compounds	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.	Day 0, Day 14