Effect of Very-low Calorie Diet and Synbiotic Supplementation in Gut Microbiota (Pronokal Method)

Study Overview
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Brief Summary
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The present study aimed to investigate the changes produced in gut microbiota by a very-low-calorie-ketogenic diet followed by a low calorie diet, whether the use of synbiotics is able to modulate gut microbiota diversity and composition and its association with gut permeability and inflammation

Detailed Description
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All participants followed a very-low-calorie ketogenic diet according to a commercial weight loss program (Pronokal method), which includes lifestyle and behavioural modification support. This method is based on high-biological-value protein preparations which contained 15 g protein, 4 g carbohydrates, 3 g fat and 50 mg docosahexaenoic acid, and provided 90-110 kcal. The study was divided in two phases. The first phase consists of a very-low-calorie ketogenic diet (600-800 kcal/day), low in carbohydrates and lipids. Throughout this ketogenic phase, supplements of vitamins and minerals such as K, Na, Mg, Ca and omega-3 fatty acids were provided. In this study the ketogenic step was maintained for 2 months. Then, the patients started a low-calorie diet (800-1500 kcal/day) which lasted two months. During the first phase consisting of a very-low-calorie ketogenic diet, subjects were randomly divided into two groups, the treatment group who received synbiotic supplementation as capsules, a complex of B. lactis, Lactobacillus rhamnosus, B. longum ES1 and prebiotics fiber (synbiotic 1) and the control group who received a placebo. During the second phase consisting of a low-calorie diet, the treatment group received synbiotic supplementation as capsules consisting of B. animalis subsp. lactis and prebiotics fiber (synbiotic 2) (synbiotic1 + synbiotic 2 group), while the control group was divided into two groups: one continued receiving a placebo (control group) whilst the other group received synbiotic 2 (placebo + synbiotic2 group).

Official Title
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Effects of Very-low Ketogenic Diet in Gut Microbiota and Its Restitution With the Use of Synbiotic Supplementation in Patients Following a Weight Loss Programme (Pronokal Method)

Conditions
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Weight Loss, Inflammation

Intervention / Treatment
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* Other: Diet
* Dietary Supplement: Synbiotic1
* Dietary Supplement: Synbiotic2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: body mass index ≥ 30 kg/m2 stable body weight in the previous 3 months Exclusion Criteria: Diabetes mellitus Obesity induced by endocrine disorders or by drugs Gastrointestinal disorders Use of antibiotics, probiotic or prebiotic agent which could modify microbiota in the previous 3 months Severe depression or any other psychiatric disease Abuse of narcotics or alcohol Severe hepatic insufficiency Any type of renal insufficiency or gout episodes Neoplasia Previous events of cardiovascular or cerebrovascular disease Renal lithiasis Uncontrolled hypertension and hydroelectrolytic alterations Females with child-bearing potential, who were pregnant, breast-feeding, intending to become pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Very low calorie ketogenic diet followed by low calorie diet | Other: Diet<br>* Very low calorie ketogenic diet followed by low calorie diet<br>|
| Experimental: Synbiotic1+synbiotic2<br>Very low calorie ketogenic diet supplemented with synbiotic 1 followed by low calorie diet supplemented with synbiotic2 | Other: Diet<br>* Very low calorie ketogenic diet followed by low calorie diet<br>Dietary Supplement: Synbiotic1<br>* B. lactis, Lactobacillus rhamnosus, B. longum ES1 and prebiotics fiber<br>Dietary Supplement: Synbiotic2<br>* B. animalis subsp. lactis and prebiotics fiber<br>|
| Experimental: placebo +synbiotic2<br>Very low calorie ketogenic diet supplemented with placebo followed by low calorie diet supplemented with synbiotic2 | Other: Diet<br>* Very low calorie ketogenic diet followed by low calorie diet<br>Dietary Supplement: Synbiotic2<br>* B. animalis subsp. lactis and prebiotics fiber<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes produced in the composition and diversity of gut microbiota by the use of synbiotics during a dietary intervention | Fecal samples were collected at baseline and at the end of dietary intervention. Fecal DNA was extracted and Gut microbiota analysis was achieved by using high-throughput sequencing | At baseline and at 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in intestinal permeability markers produced by the use of synbiotics during a dietary intervention | Blood samples were collected at baseline and at the end of study. Plasma Zonulin levels were measured by enzyme linked immunosorbent assay | At baseline and at 4 months | 
| Changes in intestinal inflammation markers produced by the use of synbiotics during a dietary intervention | Blood samples were collected at baseline and at the end of study. Plasma C-reactive protein levels were measured by enzyme linked immunosorbent assay | At baseline and at 4 months | 
| Changes in microbial translocation markers produced by the use of synbiotics during a dietary intervention | Blood samples were collected at baseline and at the end of study. Plasma lipopolysaccharide binding protein levels were measured by enzyme linked immunosorbent assay | At baseline and at 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota, obesity