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

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.

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