Long-term Effects of Arabinoxylans on Intestinal Barrier Function

Study Overview
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Brief Summary
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The higher prevalence of overweight and obesity among the population contributes to increased incidences of chronic metabolic diseases. Obesity is considered a low-grade systemic inflammatory condition through 1) production of pro-inflammatory cytokines by adipose tissue and 2) alterations in intestinal microbiota composition and associated increase in intestinal permeability. Healthcare costs related to these diseases are rising; prevention or delay of onset of disorders associated with overweight is needed. Administration of wheat arabinoxylans (NAXUS), a non-digestible carbohydrate, may change the intestinal microbiota composition and have beneficial effects on gut epithelial barrier, especially on permeability and innate immune function. Objective: To assess the effects of NAXUS on intestinal barrier function, immune system performance and metabolic control. Prebiotic properties of NAXUS will be studied. Tolerance of the product in different doses will also be investigated.

Official Title
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The Effects of Long-term Arabinoxylan Administration on Intestinal Barrier Function and Innate Immunity

Conditions
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Obesity, Overweight

Intervention / Treatment
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* Dietary Supplement: NAXUS
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overweight men/women (BMI 28-35 kg/m2) Besides overweight, healthy human beings Fasting glucose <7.0 mmol/L Normal HbA1c (4.4 to 6.2%) Consistently stable body weight for at least 6 months (± 2 kg) Exclusion Criteria: Type 2 diabetes mellitus (defined as fasting plasma glucose ≥ 7.0 mmol/L); Gastroenterological diseases or abdominal surgery; Cardiovascular diseases, cancer, liver or kidney malfunction, disease with a life expectancy shorter than 5 years; Abuse of products; alcohol (>20 alcoholic consumptions per week) and drugs Smoking Plans to lose weight or following a hypocaloric diet; Use of any medication, including vitamin supplementation, except oral contraceptives, within 14 days prior to testing; Regular use of laxation products; Use of antibiotics in the 90 days prior to the start of study. Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study Known pregnancy, lactation (checked by a pregnancy test before start of study) Blood donation within 3 months before study period Prohibited use of pro-, pre- or synbiotics during study period and three months prior to start of study. A list with forbidden products will be provided (E4 PreProbiotics). Self-admitted HIV-positive state History of any side effects towards intake of pro- or prebiotic supplements of any kind

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Maltodextrin | Dietary Supplement: Placebo<br> <br> |
| Experimental: NAXUS 7.5 grams<br>Arabinoxylan | Dietary Supplement: NAXUS<br> <br> |
| Experimental: NAXUS 15.0 grams<br>Arabinoxylan | Dietary Supplement: NAXUS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this study is to assess the change from baseline intestinal barrier function at 6 weeks, by performing a gut sugar permeability test. |  | Baseline and after 6 weeks of administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the change from baseline intestinal barrier function at 6 weeks, by assessing the tight junction structure and proteins in colonic biopsies. | Assessment will take place by immunofluorescent labelling and Polymerase Chain Reaction quantification of zonulin-1, claudin-3, occluding, myosin light chain kinase and phosphorylated myosin light chain. | Baseline and after 6 weeks of administration | 
| To assess the change from baseline local and systemic immune system performance at 6 weeks. | Secondary outcome will be measured by the expression of immune parameters in colonic biopsies, by multiplex cytokine analysis in blood and Peripheral Blood Mononuclear Cell stimulation assays. | Baseline and after 6 weeks administration | 
| To assess the change from baseline prebiotic properties at 3 and 6 weeks, by collecting faecal samples, intestinal contents and mucosal contents. | The microbial community composition, Short-chain Fatty Acid profiles in intestinal content and faeces and proteolytic activity markers in intestinal content and faeces will be determined. | Baseline, after 3 and after 6 weeks of administration | 
| To assess the change from baseline glucose and lipid metabolism at 3 and 6 weeks | By determining glucose, insulin and triglyceride in blood samples. Cholesterol and free fatty acids will be measured as part of general blood profiling. Moreover effects on insulin sensitivity will be estimated by measuring HOMA-IR. Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. | Baseline, after 3 and after 6 weeks of adminstration | 
| To assess the effect of different doses of NAXUS administration on tolerance and digestive (dys)comfort. | Via questionnaires stool frequency, stool consistency and gastrointestinal symptoms will be measured. | At baseline, after 1 wk of administration, after 2 wks of administration, after 3 wks of administration, after 4 wks of administration, after 5 wks of administration, after 6 wks of administration (in total 7 times) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prebiotics, Intestinal permeability, Gut barrier function, Immunity