Clinical trial NCT05318183: Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components
Official title: Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: PreDiabetes
Dysbiosis
Endotoxemia
Inflammation
Keywords: Gut microbiota
Microbiome
Metabolomics
Prediabetes
Glycemic response
Intestinal permeability
Gut dysbiosis
Microbiome metabolism
Whole Wheat
Phytochemicals
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: USDA Beltsville Human Nutrition Research Center
First posted: 2022-04-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be randomized to receive 4 servings per day of whole wheat bread (WWB) or white bread (WB) for 2 weeks. During each study arm, participants will be provided eucaloric standardized diets that are devoid of whole wheat products, probiotic-containing foods, and fermented foods. Before and after each study arm, a fasting blood sample and fecal sample will be obtained for metabolomic and clinical measures. Anthropometric measurements and blood pressure will be assessed at days 0, 7, and 14 of each study arm. On day 14, participants will complete an oral glucose tolerance test (OGTT) with collection of blood samples every 30 minutes for 3 hours and a simultaneous gut permeability test that entails ingesting non-digestible sugar probes and subsequent 24-h collection of urine. Upon completion of these procedures, participants will undergo a \~1 month washout before repeating the study identically, with the crossover to the alternate bread diet.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in fasting plasma glucose
timeFrame: Day 0, Day 14
Secondary outcomes:
measure: Change in plasma insulin
timeFrame: Day 0, Day 14
measure: Change in insulin sensitivity
timeFrame: Day 14
measure: Small gastrointestinal permeability
timeFrame: Day 14
measure: Colonic gastrointestinal permeability
timeFrame: Day 14
measure: Metabolic Endotoxemia
timeFrame: Day 0, Day 14
measure: Serum myeloperoxidase
timeFrame: Day 0, Day 14
measure: Level of toll-like receptor 4 gene expression
timeFrame: Day 0, Day 14
measure: Level of myeloid differentiation factor 88 gene expression
timeFrame: Day 0, Day 14
measure: Level of tumor necrosis factor alpha gene expression
timeFrame: Day 0, Day 14
measure: Level of p65 subunit of nuclear factor kappa B gene expression
timeFrame: Day 0, Day 14
measure: Level of interleukin-6 gene expression
timeFrame: Day 0, Day 14
measure: Level of interleukin-8 gene expression
timeFrame: Day 0, Day 14
measure: Level of myeloperoxidase gene expression
timeFrame: Day 0, Day 14
measure: Level of monocyte chemoattractant protein-1 gene expression
timeFrame: Day 0, Day 14
measure: Fecal calprotectin
timeFrame: Day 0, Day 14
measure: Fecal myeloperoxidase
timeFrame: Day 0, Day 14
measure: Fecal short-chain fatty acid: butyrate
timeFrame: Day 0, Day 14
measure: Fecal short-chain fatty acid: acetate
timeFrame: Day 0, Day 14
measure: Fecal short-chain fatty acid: propionate
timeFrame: Day 0, Day 14
measure: Fecal short-chain fatty acid: isobutyric acid
timeFrame: Day 0, Day 14
measure: Fecal short-chain fatty acid: isovaleric acid
timeFrame: Day 0, Day 14
measure: Serum whole wheat bread phytochemical: alkylersorcinols
timeFrame: Day 0, Day 14
measure: Serum whole wheat bread phytochemical: benoxazinods
timeFrame: Day 0, Day 14
measure: Serum whole wheat bread phytochemical: phenolic compounds
timeFrame: Day 0, Day 14
measure: Intestinal whole wheat phytochemical: alkylresorcinols
timeFrame: Day 0, Day 14
measure: Intestinal whole wheat phytochemical: benoxazinoids
timeFrame: Day 0, Day 14
measure: Intestinal whole wheat phytochemical: phenolic compounds
timeFrame: Day 0, Day 14
Other outcomes:
measure: Plasma triglyceride levels
timeFrame: Day 0, Day 14
measure: Plasma cholesterol levels
timeFrame: Day 0, Day 14
measure: Plasma HDL-cholesterol levels
timeFrame: Day 0, Day 14
measure: Serum alanine transaminase
timeFrame: Day 0, Day 14
measure: Serum inflammatory biomarker: C-reactive protein
timeFrame: Day 14
measure: Serum inflammatory biomarker: interleukin-6
timeFrame: Day 14
measure: Serum inflammatory biomarker: interleukin-8
timeFrame: Day 14
measure: Serum inflammatory biomarker: tumor necrosis factor alpha
timeFrame: Day 14
measure: Gut microbiota alpha-diversity indices
timeFrame: Day 0, Day 14
measure: Gut microbiota beta-diversity indices
timeFrame: Day 0, Day 14
measure: Gut microbiota relative abundance
timeFrame: Day 0, Day 14
Locations:
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Richard Bruno, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References: