Effect of Functional Foods on Gut Microbiota in Metabolic Syndrome

Study Overview
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Brief Summary
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Aim: To study the effect of a combination of functional foods on gut microbiota in subjects with metabolic syndrome. Subjects that met the metabolic syndrome criteria were enrolled in a double-blind, parallel-arm, placebo-control study. The subjects were randomized to receive a dietary portfolio (DP) or placebo (P) treatment for 2 mo. The primary endpoint was to study the effect of a DP on gut microbiota. Secondary endpoints were biochemical and anthropometric parameters, LPS, insulin, leptin, area under the curve for glucose and insulin.

Detailed Description
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This study was a single-center, randomized, controlled, double-blind, parallel versus placebo that consisted of five visits. The first visit was a screening evaluation to determine whether subjects met the inclusion criteria. The selected subjects were invited to a second visit that consisted of a medical history, 2-h oral glucose tolerance test (OGTT), the collection of stool samples for DNA isolation and collection of 5 ml blood sample. The participants received during the first stage, a low saturated fat diet (LSFD) for 15 days. In the third visit and second stage of dietary treatment, subjects were randomized to receive the dietary portfolio (DP) or placebo (P) treatment + an LSFD accompanied of a reduced energy diet for 1 mo. In the fourth visit, with a 1 mo interval, dietary assessment and compliance to the DP or P were evaluated. During each follow-up visit, a 24-h dietary recall was collected, a physical activity questionnaire was filled out and anthropometric and clinical parameters were assessed. In the fifth visit, a 2 -h oral glucose tolerance test (OGTT) was performed, and a stool sample for DNA isolation and 5 ml blood were collected. Dietary intervention in the first stage, the participants consumed a reduced-energy diet tailored to provide a 500-kcal/d deficit as recommended by NIH with respect to their habitual diet for 15 days. The diet plan consisted in 50-60% carbohydrates, 15% protein, 25-35% fat, <7% saturated fat, ≤ 200 mg, 20-35 g fiber, 2000 mg/d sodium based on total energy. In the second stage, the participants continued to consume the reduced energy diet with the addition of a combination of functional foods (DP). The DP provided 200 kcal that were subtracted from the diet. The DP consisted of a mixture of 14 g de dehydrated nopal, 4 g of chia, 25 g of soy protein, 14 g of oat, 4 g of inulin, 0.15 of flavoring. The placebo (P) consisted of 30 g of calcium caseinate, 30 g of maltodextrin and 0.2 g of flavoring. The kcal, appearance, and flavor were similar in DP and P. The DP and P were given in a package in the dehydrated form ready to be dissolved in water. The DP was divided into two packages, the first package contained 17.3 g of DP or P given in the breakfast and dissolved in 250 ml and the second package was given at the dinner time, and contained 34.7 g of P and DP dissolved in 300 ml of water. Dietary compliance. Dietary compliance was assessed with a 24-h dietary recall and 3-d food record (food lo), during each visit that was analyzed by food processor nutrition analysis software. The compliance of the consumption of the DP or P was evaluated with the number of empty packages returned at the following visit. Physical activity was assessed using the International physical activity questionnaire (IPAQ)

Official Title
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Effect of a Dietary Portfolio (PD) (Nopal, Chia, Soy, Oat and Inulin) and Physical Activity on Gut Microbiota in Patients With Metabolic Syndrome

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: DP
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion Criteria for controls (healthy) Male or female Adults between 20 and 60 years old BMI ≥ 20 to ≤ 25 kg/m2 Patients with no criteria positive metabolic syndrome Patients who knew how to read and write Signature of informed consent Inclusion Criteria of cases Male or female Adults between 20 and 60 years old BMI ≥ 25to ≤ 50 kg/m2 Patients with 3 positive criteria of the metabolic syndrome Glucose > 100 to < 126 mg / dl Triglycerides > 150 mg / dl HDL-cholesterol: men < 40mg / dl and women <50 mg / dl Waist circumference > 80cm in women and> 90 cm in men Blood pressure ≥ 130/85 mmHg (in two different days) Patients who knew how to read and write Signature of informed consent Exclusion Criteria: - Patients with any type of diabetes. Diseases that produce secondary obesity or diabetes Cardiovascular event Weight loss > 3 kgs in the last 3 months after the evaluation of the criteria Catabolic diseases such as cancer and acquired immunodeficiency syndrome Gravity status Positive smoking Treatment with medications Treatment with antihypertensive drugs Treatment with hypoglycemic agents or insulin and antidiabetics. Treatment with statins, fibrates or other drugs to control the dyslipidemia. Use of steroid medications, chemotherapy, immunosuppressants or radiotherapy. Anorexigens or accelerate weight loss. Any drug or medication that activates intestinal motility Laxatives or antispasmodics 4 weeks before the study Treatment with antibiotics 2 months before the study Patients with a digestive functional disorder (constipation, diarrhea, dyspepsia, functional abdominal distension) (determined by questionnaire based on the classification of Rome II). Inflammatory bowel disease Irritable bowel syndrome or other chronic gastrointestinal diseases Major surgery Treatment with pro / pre / symbiotic High fiber foods consumption (more than 15 grams of fiber)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In the first stage, the participants with metabolic syndrome consumed a reduced-energy diet tailored to provide a 500 kcal/d deficit as recommended by NIH with respect to their habitual diet for 15 days. In the second stage, the participants continued to consume the reduced energy diet with the addition of a combination of functional foods (dietary portfolio; DP). The DP provided 200 kcal that were subtracted from the diet. The kcal, appearance, and flavor were similar in DP and P. The DP and P were given in a package in a dehydrated form ready to be dissolved in water. The DP was divided into two packages, the first package contained 30 g of DP o P given in the breakfast and dissolved in 250ml and the second package was given at the dinner time and contained 30 g of P and DP dissolved in 250 mL of water.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dietary portfolio (DP)<br>The dietary portfolio was given daily at the breakfast and dinner for 2 months. The dietary intervention was a combination of functional foods (dehydrated nopal, chia seed, soy protein, oat, and inulin) that was provided in a dehydrated form in packages of 30 g dissolved in 250 ml water for breakfast and 30 g in 250ml water for dinner. | Dietary Supplement: DP<br>* a package containing a mix of functional foods<br>|
| Placebo Comparator: placebo (P)<br>The placebo (P) was given daily at the breakfast and dinner for 2 months. The placebo intervention consisted of a mixture of calcium caseinate, maltodextrins, sweetener and of artificial flavoring that was provided in a dehydrated form in packages of 30 g dissolved in 250 ml water for breakfast and 30 g in 250ml water for dinner. | Dietary Supplement: Placebo<br>* a package containing maltodextrins and caseinate calcium to mimic the DP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal microbiota | Fecal samples were collected to isolate DNA and sequenced using the Illumina platform | change after 2.5 months of dietary intervention with respect to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucose | serum glucose (mg/dl) | change after 2.5 months of dietary intervention with respect to baseline | 
| insulin | serum insulin (µU/ml) | change after 2.5 months of dietary intervention with respect to baseline | 
| glycated hemoglobin | plasma glycated hemoglobin (HbA1c) (%) | change after 2.5 months of dietary intervention with respect to baseline | 
| triglycerides | serum triglycerides (mg/dl) | change after 2.5 months of dietary intervention with respect to baseline | 
| cholesterol | serum total cholesterol (mg/dl) | change after 2.5 months of dietary intervention with respect to baseline | 
| LDL cholesterol | serum LDL- cholesterol (mg/dl) | change after 2.5 months of dietary intervention with respect to baseline | 
| HDL cholesterol | serum HDL- cholesterol (mg/dl) | change after 2.5 months of dietary intervention with respect to baseline | 
| LPS | lipopolysaccharide (LPS) (ng/ml) | change after 2.5 months of dietary intervention with respect to baseline | 
| CRP | serum C reactive protein (CRP) (mg/dl) | change after 2.5 months of dietary intervention with respect to baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolic syndrome, gut microbiota, metabolic endotoxemia, functional foods