Fiber Fermentation Kinetics Inside the Gut, and Utilization of Bacterial Metabolites

Study Overview
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Brief Summary
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In this study, the life course of SCFA and their regulatory role in human metabolism will be traced using a nose-intestine catheter. The investigators have methodological questions: investigate the envisioned kinetic profiles of stable isotope tracers of SCFAs, and to establish the time points of plasma sampling (to determine systemic availability of SCFAs). The resulting timepoints established in this pilot study will be applied during a future human intervention study.

Detailed Description
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Background: Nowadays there is a strong interest in optimising human health through manipulation of non-digestible carbohydrates (NDC). NDC are fermented by the microbiota, hereby producing fermentation end products, mainly short chain fatty acids (SCFA) acetate, butyrate, and propionate. It is hypothesized that SCFAs mediate parts of the beneficial effects of NDC. In mice, the influx of SCFA into the host correlated strongly with improvements of markers of the metabolic syndrome, whereas concentrations of SCFA in the cecum did not. The production and influx/incorporation of SCFAs in humans will be investigated. Study design: At day 1 the catheter will be placed. After an overnight fast at day 2, 5 subjects will consume a NDC bolus. Isotopically 13C-labelled SCFAs will be delivered in the cecum. Samples will be taken in the cecum and blood before, and continuously after dispensing the 13C-labelled SCFAs. Study population: 5 healthy male volunteers (18-60yrs, and BMI between 18.5-30 kg/m2). Main study parameters/endpoints: (isotopic) enrichments of SCFAs in cecum, and label incorporation in plasma metabolites such as organic acids, glucose, cholesterol, fatty acids.

Official Title
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The Study of Fiber Fermentation, and Short Chain Fatty Acid Kinetics and Utilization Inside the Gut and Systemic Circulation

Conditions
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Metabolism, Dietary Fiber, Intestine

Intervention / Treatment
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* Dietary Supplement: fructo- and galacto-oligosaccharides


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males Age 18-60yrs BMI between 18.5 and 30 kg/m2 Regular bowel movement (defaecation on average once a day) Signed informed consent Exclusion Criteria: Having a history of medical or surgical events that, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results of the study (e.g. diabetes, cardiovascular disease, gastrointestinal disease, renal failure, cancer, infectious disease, nose/throat). Use of any prescribed or non-prescribed medication (other than paracetamol) including antacids, analgesics, and herbal remedies during the three (3) weeks prior to study start. Carrying a pacemaker or any other (implanted) medical electronic device Smoker Unstable body weight (weight gain or loss >5kg in the past 3 months prior to the study start) Use of antibiotics within 3 months of starting the study or planned during the study Use of pro- or prebiotics (e.g. galacto-oligosaccharides, fructo-oligosaccharides) Constipation/infrequent bowel movement Abuse of drugs/alcohol (alcohol: >4 consumptions/day or >21 consumptions/week) Participation in another biomedical study Having diarrhoea within 2 months prior to the study start Personnel of Wageningen University, Division of Human Nutrition, their partner and their first and second degree relatives Current participation in other research from the Division of Human Nutrition Not willing to have an X-ray Having blood vessels that are too difficult for inserting a cannula Having a hemoglobin of <8.4 mmol/L

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

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: Other
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects will consume a NDC bolus. When fermentation has started, isotopically 13C-labelled SCFAs will be delivered inside the intestine. Thereafter, production and inter-conversion of SCFAs and breakdown of fiber will be studied in luminal samples. Also blood samples will be taken to study integration of the 13C-label into various metabolic compounds.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fiber drink<br>A drink high in fructo- and galacto-oligosaccharides. | Dietary Supplement: fructo- and galacto-oligosaccharides<br>* A NDC drink rich in fructo- and galacto-oligosaccharides<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of SCFAs | (13C isotopic) enrichments of SCFAs inside intestinal lumen by GC-MS | Between 0 and 10 hours | 
| Concentrations of plasma metabolites | (13-C isotopic label incorporation) in plasma metabolites by GC-MS | Between 0 and 10 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of organic acids | Organic acids measured in plasma and intestinal lumen by GC-MS | Between 0 and 10 hours | 
| Concentrations of carbohydrates | mono-, di-, tri-, oligo- and polysaccharides in the intestinal lumen by GC-MS | Between 0 and 10 hours | 
| Concentrations of metabolites in urine | bile acids, organic acids, amino acids by GC-MS | At baseline and after 10 hours | 
| Concentrations of bile acids conjugates |  | Between 0 and 10 hours | 
| Relative microbiota composition | in the intestinal lumen, via 16S rRNA sequencing | Between 0 and 10 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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short chain fatty acid, dietary fiber