The Effect of Prebiotics on Gastrointestinal Functioning and Metabolism

Study Overview
=================
Brief Summary
-----------------
The study will investigate the effect of cereal based prebiotic fibres on intestinal health and functioning and host metabolism.

Detailed Description
-----------------
A human dietary intervention study will be performed in overweight to obese subjects with a slow gastrointestinal transit time comparing the effects of a soluble prebiotic fibre vs. placebo on gut health, including gut microbiota composition, gastrointestinal transit time, metabolic health and quality of life.

Official Title
-----------------
Effect of Prebiotic Fibre on Intestinal Health and Functioning

Conditions
-----------------
Change of Transit or Circulation, Obesity

Intervention / Treatment
-----------------
* Dietary Supplement: soluble wheat bran fibre
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Overweight to obese men and women (BMI ≥ 25 kg/m2 <35 kg/m2) Aged 20-50 years Caucasian Normal fasting glucose (<6.1 mmol/L.) Normal blood pressure (systolic blood pressure 100-140 mmHg, diastolic blood pressure 60-90 mmHg) Weight stable in last 3 months (±2 kg) A low defecation frequency, <4 times/week and no constipation or underlying pathology, as determined by gastro-intestinal questionnaires). A slow whole gut transit (>35h) Exclusion Criteria: Woman lactating, pregnant (where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test) or (post)-menopausal Regular smokers People with intensive fitness training, eg. athletes (≥3 per week ≥ 1 hour training) Diabetes Mellitus (defined as FPG ≥ 7.0 mmol/l and or 2h PG ≥ 11.1 mmol/l) Gastro-intestinal diseases or abdominal surgery, cardiovascular diseases, cancer, liver or kidney malfunctioning (determined based on ALAT and creatinine levels, respectively) disease with a life expectation shorter than 5 years Following a hypocaloric diet Gluten intolerance Regular use of laxation products, or use of antibiotics, probiotics or prebiotics 3 months prior to the start of the study More than 2 symptoms occurring over a period of 12 weeks in the preceding 12 months such as Straining in >1/4 defecations; Lumpy or hard stools in >1/4 defecations; Sensation of incomplete evacuation in >1/4 defecations; Sensation of anorectal obstruction/blockade in >1/4 defecations Manual maneuvers to facilitate >1/4 defecations (e.g., digital evacuation, support of the pelvic floor); and/or <3 defecations/week Current use of medication interfering with study intervention or interfering with study endpoints/hypotheses Not to be able to understand the study information Blood donation 2 months prior to the study and during the study Participation in other studies

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 50 Years

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

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

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

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>12 weeks placebo maltodextrin 15g/day ( 5 g in beverage, to be consumed three times a day) | Dietary Supplement: Placebo<br>* 12 weeks daily intake of 15g of maltodextrin<br>* Other names: Maltodextrin;|
| Experimental: soluble wheat bran fibre<br>12 weeks soluble wheat bran fibre 15g/day (5 g in beverage, to be consumed three times a day) | Dietary Supplement: soluble wheat bran fibre<br>* 12 weeks daily intake of 15g of soluble wheat bran fibre<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole gut transit time [hours] | Whole gut transit time as measured by radio-opaque marker method | measured at baseline at week 1 and directly after the 12 week supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric emptying [min] | Gastric emptying measured by isotope breath test | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Oro-cecal transit time [min] | Oro-cecal transit time measured by hydrogen breath test | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Defecation frequency (bowel movement per day) | Defecation frequency as measured via questionnaire | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Energy expenditure | Energy expenditure measured by indirect calorimetry | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Substrate oxidation | Fat and carbohydrate oxidation measured by indirect calorimetry | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Plasma inflammatory cytokines Interleukin-6,8 and 1 (pg/ml) | IL-6, IL8,IL-1 measured by enzyme linked immunosorbent assay | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Adipose tissue gene expression | Adipose tissue gene expression measured by quantitative real time polymerase chain reaction | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Gut permeability | Gut permeability as measured by multi sugar assay | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Microbiota composition | Microbiota composition as measured by illumina sequencing in feces | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Fecal Short chain fatty acid concentrations | Fecal Short chain fatty acid concentrations measured by ion exchange chromatography with conductivity detection | measured at baseline at week 1 and directly after the 12 week supplementation | 
| Plasma short chain fatty acid concentrations | Plasma short chain fatty acid concentrations measured by liquid chromatography-mass spectrometry | measured at baseline at week 1 and directly after the 12 week supplementation |