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

Not Applicable

Completed

• Conditions: Metabolism; Dietary Fiber; Intestine
• Interventions: Dietary Supplement: fructo- and galacto-oligosaccharides

• Registration Number: NCT04013607
• Lead Sponsor: Wageningen University

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.

Study Timeline

• Study First Submitted: 2019-04-23
• Study First Submitted QC: 2019-07-04
• Study Start: 2019-07-08
• Study First Posted: 2019-07-10
• Primary Completion: 2019-10-17
• Study Completion: 2019-10-17
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-12
• Last Update Posted: 2020-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fiber drink	fructo- and galacto-oligosaccharides	A drink high in fructo- and galacto-oligosaccharides.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

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

Trial Locations

Locations (1)

Wageningen University; 🇳🇱 Wageningen, Gelderland, Netherlands