In this pilot study we have technical/methodological questions: we want to confirm the envisioned kinetic profiles of stable isotope tracers 13C-labelled SCFA delivered by catheter in 5 subjects, and to establish the time points of plasma sampling (…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
microbiota compositie activiteit en microbiële producten
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: (isotopic) enrichments of SCFAs (in the cecum
and blood), and plasma organic acids, glucose, cholesterol, fatty acids
Secondary outcome
Blood markers for microbial activity: Markers of specific microbial group
activity that can be related to the host health status, like organic acids,
hippurate, di- en tri-methylamine, acetaldehydes, glucuronic acid conjugates,
and bile acid (conjugates).
Bacterial activity/microbiota composition in luminal samples.
Fibre degradation: To study acute fibre breakdown, the fibre degradation
products, including mono-, di-, tri-, oligo- and polysaccharides.
Urine metabolic profiles: A fasting urine sample will be collected before at
the start of the test day and at the end of the test day. Urine samples will be
analysed to analyse bile acids, organic acids, aminoa cids, including bacterial
products and their taurine, glycine, and glucuronic acid conjugates.
Background summary
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.
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 of intestinal chyme.
Study objective
In this pilot study we have technical/methodological questions: we want to
confirm the envisioned kinetic profiles of stable isotope tracers 13C-labelled
SCFA delivered by catheter in 5 subjects, and to establish the time points of
plasma sampling (to determine systemic availability of SCFAs). Additionally, we
want to test the proper time delay between delivery, and sampling of
13C-labelled SCFAs inside the cecum using the same catheter, to study
interconversions of SCFA in the human gut. The resulting timepoints established
in this pilot study will be applied during a future human intervention study in
which the impact of a contrast in dietary NDC will be investigated.
Study design
In the cecum isotopically 13C-labelled SCFAs will be delivered, afterwards at
different time points samples will be taken from the cecum and blood. In short:
at day 1 the catheter will be placed, and afterwards participants stay maximum
7 hours in the hospital, to ensure progression of the nose-intestine catheter
towards the distal small intestine. After an overnight fast at day 2, 5
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 8 hours. When
fermentation has started, isotopically 13C-labelled SCFAs will be delivered in
the cecum. Thereafter, production and inter-conversion of SCFAs and breakdown
of fiber, will be studied in luminal samples that will be taken every 30 min to
determine SCFA cross-feeding. We sample in the cecum at different times to
select the best time point to study cross-feeding in the final human
intervention study. Blood samples will be collected from a cannula before, and
continuously after dispensing the 13C-labelled SCFAs.
Intervention
200 mL tap water, 5 gram fructo-oligosaccharides, 5 gram
galacto-oligosaccharides, non-absorbable marker PEG-4000
Study burden and risks
Subjects that participate in this study will invest approximately 23.5 hours.
The subjects will perceive mild discomfort during the placement of the
catheter. The radiation exposure is minimal (0.12 mSv) and induces no health
risk to the healthy subjects. In case of structural complains we will council
our medical supervisor. The GOS and FOS present in the NDC bolus are
commercially available and of food-grade quality (provided by FrieslandCampina
and Sensus B.V.). During the test day (takes around 12 hours) we will collect
200ml of blood. The Hb value of each participants will be checked before blood
collection. Participants will have to visit the Hospital Gelderse vallei at two
occasions. Participants will receive ¤320,- after completion of the study, they
will also receive a repayment of traveling expenditures for the visit, and for
the screening ¤10.
Stippeneng 4
Wageningen 6708 WE
NL
Stippeneng 4
Wageningen 6708 WE
NL
Listed location countries
Age
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).
* Having a history of surgical events of the gastro-intestinal tract (e.g.
bariatric surgery/gastric bypass surgery).
• Presence of swallowing disorder
• 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.
• Use of cholesterol lowering medication
• 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 undergo fluoroscopy
• Having blood vessels that are too difficult for inserting a venflon
* Having a hemoglobin of <8.4 mmol/L
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL69449.081.19 |