Fiber Fermentation, and Short Chain Fatty Acid Kinetics and Utilization Inside the Gut and Systemic Circulation

Not Applicable

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

• Registration Number: NCT04499183
• Lead Sponsor: Wageningen University

Brief Summary

Nowadays there is a strong interest in optimising human health through manipulation of non-digestible carbohydrates (NDC). NDC can be used as substrates by gut microbiota, which results in NDC degradation, production of fermentation products, such as short-chain fatty acids (SCFA), and a shift in microbiome composition and activity. 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, in contrast to the concentrations of SCFA in the proximal colon. Therefore, the influx of short chain fatty acids (SCFA) into the body may be of high importance in improving metabolism. There is a need for more studies in humans to trace the life course of SCFA and their regulatory role in human metabolism. To study this inner world of bacterial products in humans, we will use a nasal-intestine catheter that can be used for delivery of components and sampling chyme in the proximal colon. Before the proposed methodology can be applied in a large intervention study, a small scale feasibility study needs to be performed that addresses colonic placement of the nasal-intestine cathether and colonic sampling of regular and NDC-enriched chyme samples. We will investigate the acute fermentation of fructo- and galacto-oligosaccharides in the proximal colon. Moreover, we will deliver 13C-labelled SCFA via a naso-intestinal catheter to quantify the fluxes of SCFA production, interconversion and uptake by the host. A small-scale, 7-day parallel feasibility trial, N=5 subjects will receive GOS/FOS supplements (mix 1:1 ratio, 15 gram/day), and N=5 other subjects will receive placebo supplements (isocaloric maltodextrin, 12 gram/day). At the last day of the supplementation period, the catheter will be placed, and afterwards participants stay maximum 5 hours in the hospital, to ensure progression of the nose-intestine catheter. After an overnight fast, subjects will visit the hospital again for measurements. Subjects will consume a NDC bolus (200 mL tap water, 5 gram fructo-oligosaccharides, 5 gram galacto-oligosaccharides, non-absorbable marker (PEG-4000). Afterwards, they are not allowed to eat for 6.5 hours. Isotopically 13C-labelled SCFAs will be delivered in the proximal colon. Blood and colonic luminal samples, breath samples, faeces and urine will be collected.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-26
• Study First Submitted QC: 2020-07-30
• Study First Posted: 2020-08-05
• Status Verified: 2020-10
• Study Start: 2020-10-08
• Last Update Submitted: 2020-10-12
• Last Update Posted: 2020-10-19
• Primary Completion: 2021-02-01
• Study Completion: 2021-02-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
non-digestible carbohydrates	fructo- and galacto-oligosaccharides	fructo- and galacto-oligosaccharides
placebo	fructo- and galacto-oligosaccharides	maltodextrin

Primary Outcome Measures

Name	Time	Method
Concentrations of carbohydrates	Between 0 and 400 minutes	mono-, di-, tri-, oligo- and polysaccharides in the intestinal lumen
Catheter placement in the colon	After 1 week	To show placement of a naso-intestinal catheter in the proximal colon.
Relative microbiota composition and metabolites	Between 0 and 400 minutes	Microbiota and metabolites inside the intestine
Concentrations of SCFAs	Between 0 and 400 minutes	(13C isotopic) enrichments of SCFAs inside intestinal lumen
Concentrations of plasma metabolites	Between 0 and 400 minutes	organic acids, amino acids, glucose, cholesterol, fatty acids and bile acids in blood
Volume of colon sample (mL)	Between 0 and 400 minutes	To check whether enough material for analysis is obtained if the catheter system takes samples in the proximal colon of participants.

Secondary Outcome Measures

Name	Time	Method
Questionnaires about (dis)comfort of study procedures	After 1 week	Questions about study procedures
Concentrations of urine metabolites	After 0 and 120 minutes	hippurate, di- en tri-methylamine, acetaldehydes, taurine, glycine, glucuronic acid conjugates, and bile acid profiles (conjugates)
Relative microbiota composition and metabolite concentrations	After 1 week	Microbiota and metabolome in faeces

Trial Locations

Locations (1)

Wageningen University and Research; 🇳🇱 Wageningen, Netherlands