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

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

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.

Study Overview

• Status: Completed
• Conditions: Metabolism; Dietary Fiber; Intestine
• Intervention / Treatment: Dietary supplement: fructo- and galacto-oligosaccharides

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 Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Wageningen, Gelderland, Netherlands, 6708 WE
      • Wageningen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fiber drink; A drink high in fructo- and galacto-oligosaccharides.	Dietary supplement: fructo- and galacto-oligosaccharides; A NDC drink rich in fructo- and galacto-oligosaccharides

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: University Medical Center Groningen
• Investigators: Principal Investigator: Guido Hooiveld, PhD, Wageningen University

Publications and helpful links

General Publications

• den Besten G, Havinga R, Bleeker A, Rao S, Gerding A, van Eunen K, Groen AK, Reijngoud DJ, Bakker BM. The short-chain fatty acid uptake fluxes by mice on a guar gum supplemented diet associate with amelioration of major biomarkers of the metabolic syndrome. PLoS One. 2014 Sep 9;9(9):e107392. doi: 10.1371/journal.pone.0107392. eCollection 2014.
• den Besten G, Lange K, Havinga R, van Dijk TH, Gerding A, van Eunen K, Muller M, Groen AK, Hooiveld GJ, Bakker BM, Reijngoud DJ. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am J Physiol Gastrointest Liver Physiol. 2013 Dec;305(12):G900-10. doi: 10.1152/ajpgi.00265.2013. Epub 2013 Oct 17.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2019
• Primary Completion (Actual): October 17, 2019
• Study Completion (Actual): October 17, 2019

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: July 4, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 12, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: dietary fiber; short chain fatty acid
• Other Study ID Numbers: NL69449.081.19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Collected data will be coded

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No