Effect of Dietary Flavonoids on Intestinal Microbiota, Intestinal Inflammation and Metabolic Syndrome

Study Overview
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Brief Summary
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The investigators have hypothesized that dietary flavonoids reduce insulin resistance and subclinical inflammation secondary to reductions in intestinal inflammation and permeability and that these events are mediated through alterations in gut microbiota composition. To test this hypothesis, 30 overweight/obese men and women will be provided two well-controlled diets that are identical in macronutrient content (Protein, 17% en; Fat, 30% en; Carbohydrate, 53% en), but differ markedly in flavonoid content (Low Flavonoid Diet, 10 mg/1000 Kcals; High Flavonoid Diet, 340 mg/1000 Kcals). All meals for both diets will be prepared and fed for 6 weeks each in a randomized cross-over design with endpoints determined in duplicate during the last week of each diet period.

Official Title
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Effect of Dietary Flavonoids on Intestinal Microbiota, Intestinal Inflammation and Metabolic Syndrome

Conditions
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Metabolic Syndrome X, Inflammation

Intervention / Treatment
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* Other: High Dietary Flavonoids
* Other: Low Dietary Flavonoids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 25 and 35 kg/m2 Exclusion Criteria: Documented presence of atherosclerotic disease; Diabetes mellitus Uncontrolled hypertension Renal, hepatic, endocrine, gastrointestinal or other systemic disease For women, pregnancy, breast feeding or postpartum < 6 months History of drug or alcohol abuse History of depression or mental illness requiring hospitalization within the last 12 months Use of antibiotics within the last 6 months Multiple food allergies or significant food preferences or restrictions that would interfere with diet adherence Chronic use of over-the-counter medication which would interfere with study endpoints including NSAIDS, laxatives and antacids Lifestyle or schedule incompatible with the study protocol Other medical, psychiatric, or behavioral conditions that in the view of the principal investigator may present a safety hazard to the participant or interfere with study participation or the ability to follow the intervention protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Flavonoids then High Flavonoids<br>Participants receive a prepared diet with Low Dietary Flavonoids (10 mg of flavonoids/1000 Kcals) for six weeks. After a minimum washout period of 2 weeks, participants receive a prepared diet with High Dietary Flavonoids (340 mg of flavonoids/1000 Kcals) for six weeks. | Other: High Dietary Flavonoids<br>* A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing high levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.<br>Other: Low Dietary Flavonoids<br>* A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing low levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.<br>|
| Experimental: High Flavonoids then Low Flavonoids<br>Participants receive a prepared diet with High Dietary Flavonoids (340 mg of flavonoids/1000 Kcals) for six weeks. After a minimum washout period of 2 weeks, participants receive a prepared diet with Low Dietary Flavonoids (10 mg of flavonoids/1000 Kcals) for six weeks. | Other: High Dietary Flavonoids<br>* A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing high levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.<br>Other: Low Dietary Flavonoids<br>* A prepared diet consisting of whole foods with a macronutrient composition of 17% en from protein, 30% en from fat and 53% energy from carbohydrate and containing low levels of dietary flavonoids including anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polyflavonoids.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal calprotectin | Primary endpoint for intestinal inflammation | 6 weeks | 
| Serum C-reactive protein | One of two primary endpoints for systemic inflammation | 6 weeks | 
| Serum soluble tumor necrosis factor receptor-1 | One of two primary endpoints for systemic inflammation | 6 weeks | 
| Serum insulin | Primary endpoint for insulin resistance | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal microbiome composition | Includes relative abundances of operational taxonomic units and assigned taxonomy as well as alpha and beta diversity measurements | 6 weeks | 
| Fecal short chain fatty acids | Measure of fecal microbiome metabolic capabilities and includes acetate, propionate, butyrate, valerate and caproate. | 6 weeks | 
| Fecal eosinophil protein X | Secondary endpoint for intestinal inflammation | 6 weeks | 
| Fecal myeloperoxidase | Secondary endpoint for intestinal inflammation | 6 weeks | 
| Intestinal permeability by four sugar differential absorption test | Secondary endpoint for intestinal inflammation | 6 weeks | 
| Serum endotoxin | Secondary endpoint for intestinal inflammation | 6 weeks | 
| Serum interleukin-6 | Secondary endpoint for systemic inflammation | 6 weeks | 
| Serum soluble tumor necrosis factor receptor-2 | Secondary endpoint for systemic inflammation | 6 weeks | 
| Serum fasting glucose | Secondary endpoint for insulin resistance | 6 weeks | 
| Calculated Homeostatic Model Assessment-Insulin Resistance | Secondary endpoint for insulin resistance | 6 weeks | 
| Serum C-peptide | Secondary endpoint for insulin resistance | 6 weeks | 
| Plasma lipids | Secondary endpoint for insulin resistance. Includes LDL-cholesterol, HDL-cholesterol and triglycerides | 6 weeks | 
| Blood pressure | Secondary endpoint for insulin resistance. Includes systolic and diastolic blood pressure | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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flavonoids, insulin resistance, plasma lipids, intestinal microbiome, intestinal inflammation, subclinical inflammation