Clinical trial NCT04013607: Fiber Fermentation Kinetics Inside the Gut, and Utilization of Bacterial Metabolites
Official title: The Study of Fiber Fermentation, and Short Chain Fatty Acid Kinetics and Utilization Inside the Gut and Systemic Circulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolism
Dietary Fiber
Intestine
Keywords: short chain fatty acid
dietary fiber
Lead sponsor: Wageningen University
Sponsor class: OTHER
Collaborators: name: University Medical Center Groningen
First posted: 2019-07-10
Enrollment: 5
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Concentrations of SCFAs
timeFrame: Between 0 and 10 hours
measure: Concentrations of plasma metabolites
timeFrame: Between 0 and 10 hours
Secondary outcomes:
measure: Concentrations of organic acids
timeFrame: Between 0 and 10 hours
measure: Concentrations of carbohydrates
timeFrame: Between 0 and 10 hours
measure: Concentrations of metabolites in urine
timeFrame: At baseline and after 10 hours
measure: Concentrations of bile acids conjugates
timeFrame: Between 0 and 10 hours
measure: Relative microbiota composition
timeFrame: Between 0 and 10 hours
Other outcomes:
Locations:
city: Wageningen
country: Netherlands
facility: Wageningen University
state: Gelderland
Study officials:
affiliation: Wageningen University
name: Guido Hooiveld, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.