Effect of a Synbiotic on the Gut Microbiota and Adiposity-related Markers in Healthy Overweight Subjects

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of a synbiotic (ProSynbiotic) on the gut microbiota composition, body composition and adiposity-related genes and metabolic markers in healthy overweight adult subjects.

Detailed Description
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This is a parallel, double-blind, randomized, placebo controlled trial to determine the effects of a synbiotic formulation (ProSynbiotic) containing 4 billion CFU of a probiotic blend of Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5, Lactobacillus casei 431 and Saccharomyces boulardii, along with 1 g of the prebiotic inulin and 100 mg of galactooligosaccharide (GOS) on the gut microbiota composition, body composition, expression of genes mediating dietary energy harvest and adiposity, and on adiposity-related metabolic markers in healthy free-living overweight or moderately obese subjects. The duration of the study is 18 weeks, including a 2-week run-in period before randomization of subjects into the synbiotic or placebo group, a 12-week intervention period, and a 4-week follow-up after the end of the intervention. During the intervention period, subjects will be instructed to take 3 capsules of either synbiotic or placebo per day and maintain their habitual diet and physical activity. They will also be asked to document any unusual symptoms or side effects as well as keep a bowel diary. Diet and physical activity will be monitored via 24-h dietary recalls and the global physical activity questionnaire respectively. Changes in the gut microbiota composition will be determined by measuring bacterial population levels in stool sampled collected at baseline, 6 weeks, 12 weeks and the follow up time point. Body composition will be measured using the BOD POD at baseline, 6 weeks, and 12 weeks. Gene expression levels will be assessed at baseline and 12 weeks in colonocytes (isolated from stool samples) and PBMCs (isolated from blood samples) by qPCR. Metabolic markers will be measured at baseline and 12-weeks in plasma or serum using the respective biochemical- or immuno-assays.

Official Title
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Pilot Study on the Influence of a Synbiotic Formulation (ProSynbiotic) on Gut Microbiota Composition, Adiposity and Selected Markers of Cardiometabolic Health in Overweight or Moderately Obese Individuals

Conditions
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Adiposity, Gut Microbiota

Intervention / Treatment
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* Dietary Supplement: Synbiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18-64 BMI of 25-34.9 and/or a waist circumference >35 inches for women and >40 inches for men Generally healthy except for overweight or moderately obese A signed consent form Passed a screening questionnaire and willingness to comply with study procedures Lipid levels, fasting glucose, liver function and complete blood counts within the normal reference ranges as measured in a screening blood sample Exclusion Criteria: Persons on a weight-loss regimen Antibiotic use (< 3 months before the study) Regular probiotic, prebiotic or synbiotic use (< 1 month before the study) Regular use of anti-inflammatory drugs, weight-loss medications or supplements (< 1 month prior to the study) Personal history of cardiovascular disease, hypertension, cancer, type 1 or type 2 diabetes and inflammatory gastrointestinal disorders such as Crohn's disease or colitis Smoking Consumption of >2 units of alcohol per day Pregnancy or lactation Irregular periods, menopause or hormone replacement therapy Over 300 minutes of exercise per week

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synbiotic<br>3 capsules per day containing 4 billion CFU of Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5, Lactobacillus casei 431 and Saccharomyces boulardii in combination with prebiotics Inulin (1 g) and Galactooligosaccharides (100 mg) | Dietary Supplement: Synbiotic<br>* 3 capsules per day containing 4 billion CFU of Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5, Lactobacillus casei 431 and Saccharomyces boulardii in combination with prebiotics Inulin (1 g) and Galactooligosaccharides (100 mg)<br>* Other names: Prosynbiotic;|
| Placebo Comparator: Placebo<br>3 capsules of Maltodextrin per day | Other: Placebo<br>* 3 capsules of Maltodextrin per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes to the gut microbiota | The primary objective of this study is to determine the effect of a synbiotic formulation called ProSynbiotic (administered at 3 capsules/day) containing 4 billion CFU of a probiotic blend of Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5, Lactobacillus casei 431 and Saccharomyces boulardii, along with 1 g of the prebiotic inulin and 100 mg of galactooligosaccharide (GOS) on the gut microbiota of healthy overweight adult subjects when compared to a placebo of maltodextrin. Changes in the gut microbiota will be determined by measuring specific bacterial population levels in the subjects' fecal samples, using 16S rRNA targeted oligonucleotide probes and fluorescence in situ hybridisation. | 0-weeks (Baseline), 6-weeks (midpoint of intervention), 12-weeks (end of intervention) and 16-weeks (4-weeks after end of intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | The effect of Prosynbiotic on the subjects' body composition will be evaluated by BOD POD assessment carried out at baseline, 6-weeks and 12-weeks. | Baseline, 6-weeks and 12-weeks. | 
| Expression of genes mediating dietary energy harvest and adiposity | This will be achieved by measuring the gene expression levels of ANGPTL4, PPAR-γ and GPR41/43 in colonocytes isolated from stool and that of ANGPTL4, PPAR-γ, NF-kB, IL-6 and TNF-α in PBMCs isolated from blood collected from the subjects at baseline and 12-weeks. | Baseline and 12-weeks | 
| Adiposity-related metabolic markers | This will be achieved by measuring TNF-α, adiponectin, total cholesterol, LDL-C, HDL-C, triglycerides and glucose levels in fasting blood samples collected from the study subjects at baseline and 12-weeks. | Baseline and 12-weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GOS, Gut microbiota, Probiotics, Prebiotics, Synbiotic, Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5, Lactobacillus casei 431, Inulin, Body Weight, Overweight, Adiposity, Obesity, ANGPTL4