The Effect of Prebiotic Fibres on Weight Loss in an Overweight and Obese Population

Study Overview
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Brief Summary
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The aim of this study is to investigate whether a diet supplemented with two prebiotic fibres induces greater changes in body weight compared to placebo during 12 weeks of energy restriction in an obese/overweight population. The hypothesis is that the fiber-containing dietary supplement will: 1) Induce greater changes in body weight compared to the placebo group 2) change the gut microbiota composition 3) improve glucose homeostasis 4) decrease serum concentration of triglycerides, total and LDL cholesterol The hypothesis is that the effect of the intervention on weight loss will be partly mediated by the diet-induced changes in the gut microbiota composition.

Detailed Description
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Prebiotics are nutrients that specifically utilized by the gut microbiota. Beneficial health effects of prebiotics are generally attributed to 1) stimulation of beneficial bacteria and SCFA production, and consequently; improved barrier function, regulation of enteroendocrine peptide secretion and resistance to inflammatory stimuli; 2) modulation of lipid metabolism, possibly by suppression of lipogenic enzymes and thus decreased synthesis of lipoproteins and triglycerides; and 3) increased mineral absorption. Inulin is recognized as a common prebiotic. Fibersol-2 is a resistant starch that has been suggested to induce satiety, when given in a dose of 10 g. Intake of inulin has been shown to induce changes in the microbial abundance and increase production of SCFA19; whereas resistant starch has been shown to improve insulin sensitivity and postprandial glucose AUC20. However, the effects of an intervention with a combination of these two fibers on obesity and body composition during an energy restricted diet have not been addressed. Supplements with other types of fibres in addition to energy restriction have shown additional effects in weight reduction. In this study, the effects of a combination product of two prebiotic fibres on additional weight loss during energy restriction in a placebo-controlled, randomized parallel study with a duration of 12 weeks will be tested. Furthermore, the effects of the fibres on the gut microbial composition, markers of metabolic syndrome (MetS) and glucose metabolism will be tested. The active diet will contain intervention products high in dietary fibre and the placebo diet will contain maltodextrin. The fiber-containing dietary supplements will add approximately 20 g of prebiotic fibres per day, where approximately 10 g will be inulin and approximately 10 g will be resistant maltodextrin. The intervention products and placebo will be consumed as milk. The fiber-containing dietary supplement is expected to induce additional weight loss, compared to placebo and to affect the gut microbiome and markers of metabolic disease.

Official Title
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Effects of a Combination of Prebiotic Fibres on Weight Loss During an Energy Restricted Diet in an Overweight/Obese Population

Conditions
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Obesity

Intervention / Treatment
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* Dietary Supplement: Fiber-containing dietary supplement
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI: 28-45 kg/m2 Non-smoking Haemoglobin level ≥7 mmol/L Exclusion Criteria: Use of antibiotics three months prior to study and during the study. If a participant uses antibiotics prior to randomization, the participant will be invited to be re-screened 3 months after the last use of antibiotics, provided that it is realistic to complete the study no later than the scheduled LPLV Weight change >3 kg two months prior to study Blood donation other than for this study <1 month prior to study and during study. Participation in clinical trials other than for this <1 month prior to study and during study Intensive physical training/ elite athlete (>10 hours of strenuous physical activity per week) Unstable medication for dyslipidaemia and elevated blood pressure (the participant must have had a stable dose in the three months prior to study start), and use of systemic glucocorticoids Medication for T2D Treatment with metformin Dietary supplements with pro- and/or prebiotics and/or fibre 6 weeks prior to study Special dietary regimen (vegetarians, vegans etc.), as evaluated by study staff Lactose intolerance or allergy to components in the intervention products Gluten intolerance Maltodextrin intolerance Lactation, pregnancy or planning of pregnancy during the study Gastro intestinal and liver disorders Chronic inflammation disorders (excluding obesity) Diagnosed psychiatric disorder including depression requiring treatment Surgical treatment of obesity and abdominal surgery Inability, physically or mentally, to comply with the procedures required by the study protocol, as evaluated by the study staff

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fiber-containing dietary supplement<br>2 x 200 ml of fiber-enriched UHT milk during 12 weeks of energy restriction | Dietary Supplement: Fiber-containing dietary supplement<br>* Effects of fiber-containing dietary supplement on weight loss during energy restriction<br>|
| Placebo Comparator: Placebo<br>2 x 200 ml of UHT milk with maltodextrin during 12 weeks of energy restriction | Dietary Supplement: Placebo<br>* Effects of placebo supplement on weight loss during energy restriction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight loss | Differences in changes in body weight between the group that receives fiber-containing dietary supplement and placebo group | Measurements will be performed at baseline and after 12 weeks of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Changes in body composition | Measurements will be performed at baseline and after 12 weeks of intervention | 
| Gut microbiota composition and function | Changes in gut microbiota composition and function (faecal samples) assesed by metagenomics | Measurements will be performed at baseline and after 12 weeks of intervention | 
| Glucose metabolism | Glucose and insulin homeostasis | Measurements will be performed at baseline and after 12 weeks of intervention | 
| Lipid metabolism | Analyses of lipids in blood samples | Measurements will be performed at baseline and after 12 weeks of intervention | 
| Inflammatory markers | Changes in concentration of inflammatory markers | Measurements will be performed at baseline and after 12 weeks of intervention | 
| SCFA concentration | Changes in faecal concentration of short chain fatty acids | Measurements will be performed at baseline and after 12 weeks of intervention | 
| Lipidomics and bile acids | Changes in concentration of lipids and bile acids in blood and faecal samples | Measurements will be performed at baseline and after 12 weeks of intervention | 
| Metabolomics | Analyses of metabolites in blood, urine and fecal samples | Measurements will be performed at baseline and after 12 weeks of intervention | 
| Weight loss | Interaction between differences in changes in body weight between the group that receives fiber-containing dietary supplement and placebo group and each of baseline fasting glucose, baseline fasting insulin and baseline microbiome composition (e.g. enterotype). | Measurements will be performed at baseline and after 12 weeks of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prebiotics, Microbiome, Glucose metabolism