Effect of Cranberry and Agaves Extract on Microbiota and Intestinal Health

Study Overview
=================
Brief Summary
-----------------
The growing prevalence of obesity and type 2 diabetes (T2D) is a major public health problem. Recent studies have clearly established that the gut microbiota plays a key role in the investigator's propensity to develop obesity and associated metabolic health disorders. The gut microbiota compositions plays a decisive role in glucose metabolism and the chronic inflammatory state associated with insulin resistance. Consuming prebiotic rich diet, including polyphenol and inulin rich food could help modulate favorably the gut microbiota which could lead to a reduction of endotoxemia and beneficial metabolic health effects.

Detailed Description
-----------------
It is now recognized that overweight individuals have altered microbiota which could lead to intestinal barrier defects and chronic inflammation disorders. Polyphenols such as Proanthocyanidins may modulate the gut microbiota thereby providing beneficial effects on metabolic health. Inulin is a well known prebiotic that could stimulate growth of favorable bacteria in the gut. The overall goal is to determine the efficacy and synergy of a supplement of polyphenols from cranberry extract with or without a supplement of inulin from agaves to reduce chronic inflammation and endotoxemia and to improve glucose metabolism and insulin sensitivity by modulating microbiota of overweight human subjects with metabolic syndrome symptoms.

Official Title
-----------------
Prebiotic Supplementation and Metabolic Endotoxemia and Modulation of the Gut Microbiota: Double-blind and Randomized Parallel Clinical Study of the Efficacy and Synergistical Effect of Cranberry Polyphenols and Inulin From Agaves

Conditions
-----------------
Endotoxemia, Metabolic Syndrome, Glucose Metabolism Disorders, Insulin Resistance

Intervention / Treatment
-----------------
* Dietary Supplement: Cranberry
* Dietary Supplement: Agaves
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: overweight (BMI 25-39.9 kg/m2) or waist circumference ≥ 80 cm (women) and ≥94 cm (men) fasting insulin over 60 pmol/L or fasting glucose 5.6 - 6.9 mmol/L at least one of the following criteria: Tg ≥ 1.7 mmol/L; blood pressure ≥ 130/85 mmHg; HDL < 0,9 mmol/L; hsCRP 1-10 mg/L non-smoking eating fruits and vegetables less then 5 portions/day Exclusion Criteria: chronic disease taking drugs or natural health products that could affect glucose or lipid metabolism taking anti-inflammatory, antiacids taking pre or probiotics inflammatory bowel disease antibiotics in the past 3 months allergy or intolerance to cranberries or agaves Major surgery in the past 3 months

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cranberry and Agaves<br>Cranberry extract (2 capsules) + Agaves powder (1 single-dose packet) | Dietary Supplement: Cranberry<br>* Supplementation of polyphenols from cranberry extract<br>Dietary Supplement: Agaves<br>* Supplementation of inulin from Agaves powder<br>|
| Experimental: Cranberry and placebo<br>Cranberry extract (2 capsules) + Placebo powder (1 single-dose packet) | Dietary Supplement: Cranberry<br>* Supplementation of polyphenols from cranberry extract<br>Dietary Supplement: Placebo<br>* Supplementation with placebo<br>|
| Experimental: Placebo and Agaves<br>Placebo (2 capsules) + Agaves powder (1 single-dose packet) | Dietary Supplement: Agaves<br>* Supplementation of inulin from Agaves powder<br>Dietary Supplement: Placebo<br>* Supplementation with placebo<br>|
| Placebo Comparator: Placebo and placebo<br>Placebo (2 capsules) + Placebo powder (1 single-dose packet) | Dietary Supplement: Placebo<br>* Supplementation with placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in metabolic endotoxemia: Measure concentration of Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP) in plasma | effect of the supplements on variation in plasma concentration of LPS and LBP | At the beginning and the end of treatment (10 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in intestinal permeability: Measure concentration of zonulin in plasma | effect of the supplements on plasma concentration of zonulin | At the beginning and the end of treatment (10 weeks) | 
| Change in inflammation state of the tissue: Measure concentration of calprotectin and lactoferrin in feces | effect of the supplements on fecal calprotectin and lactoferrin | At the beginning and the end of treatment (10 weeks) | 
| Change in systemic inflammation: Measure concentration of inflammation biomarkers in the serum | effect of the supplements on chronic inflammation (serum concentration of hsCRP, Il-6, TNF-alpha, IL-1 beta, IL-23) | At the beginning and the end of treatment (10 weeks) | 
| Change in glucose serum concentration | effect of the supplements on serum concentration of glucose | At the beginning and the end of treatment (10 weeks) | 
| Change in insulin and C-peptide serum concentration | effect of the supplements on serum concentration of insulin and C-peptide | At the beginning and the end of treatment (10 weeks) | 
| Change in microbiota diversity: growth of Akkermancia muciniphila, Lactobacillus, Prevotella, Bifdobacterium and inhibition of Clostridium perfringens, C. difficile, Bacteroides spp.) | Global variation of the fecal microbiota and gut microbiota profiling | At the beginning and the end of treatment (10 weeks) |