Dietary Fiber, Intestine, Metabolism
Conditions
Keywords
short chain fatty acid, dietary fiber
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTfructo- and galacto-oligosaccharides
A NDC drink rich in fructo- and galacto-oligosaccharides
Sponsors
University Medical Center Groningen
Wageningen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of SCFAs | Between 0 and 10 hours | (13C isotopic) enrichments of SCFAs inside intestinal lumen by GC-MS |
| Concentrations of plasma metabolites | Between 0 and 10 hours | (13-C isotopic label incorporation) in plasma metabolites by GC-MS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of metabolites in urine | At baseline and after 10 hours | bile acids, organic acids, amino acids by GC-MS |
| Concentrations of organic acids | Between 0 and 10 hours | Organic acids measured in plasma and intestinal lumen by GC-MS |
| Relative microbiota composition | Between 0 and 10 hours | in the intestinal lumen, via 16S rRNA sequencing |
| Concentrations of bile acids conjugates | Between 0 and 10 hours | — |
| Concentrations of carbohydrates | Between 0 and 10 hours | mono-, di-, tri-, oligo- and polysaccharides in the intestinal lumen by GC-MS |
Countries
Netherlands
Outcome results
None listed