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

Metabolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04013607
• Other study ID #: NL69449.081.19
• Status: Completed
• Phase: N/A
• Start date: July 8, 2019
• Est. completion date: October 17, 2019

Study information

• Verified date: October 2020
• Source: Wageningen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: October 17, 2019
• Est. primary completion date: October 17, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Dietary Fiber
• Intestine
• Metabolism

Intervention

Dietary Supplement:
• fructo- and galacto-oligosaccharides
A NDC drink rich in fructo- and galacto-oligosaccharides

Locations

Country	Name	City	State
Netherlands	Wageningen University	Wageningen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Wageningen University	University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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. — View Citation

den Besten G, Lange K, Havinga R, van Dijk TH, Gerding A, van Eunen K, Müller 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentrations of SCFAs	(13C isotopic) enrichments of SCFAs inside intestinal lumen by GC-MS	Between 0 and 10 hours
Primary	Concentrations of plasma metabolites	(13-C isotopic label incorporation) in plasma metabolites by GC-MS	Between 0 and 10 hours
Secondary	Concentrations of organic acids	Organic acids measured in plasma and intestinal lumen by GC-MS	Between 0 and 10 hours
Secondary	Concentrations of carbohydrates	mono-, di-, tri-, oligo- and polysaccharides in the intestinal lumen by GC-MS	Between 0 and 10 hours
Secondary	Concentrations of metabolites in urine	bile acids, organic acids, amino acids by GC-MS	At baseline and after 10 hours
Secondary	Concentrations of bile acids conjugates		Between 0 and 10 hours
Secondary	Relative microbiota composition	in the intestinal lumen, via 16S rRNA sequencing	Between 0 and 10 hours