In this trial we now aim to investigate comprehensively the effect of riboflavin supplementation on the abundance of F. prausnitzii and on other members of the gut microbiota in faeces of healthy volunteers. Additionally we will assess whether…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Healthy Intestinal Microbiota
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the effect of 2 weeks oral riboflavin supplementation (50 and 100
mg/day) on the number of F. prausnitzii per gram faeces in comparison with
placebo.
Secondary outcome
1. To determine the effect of 2 weeks oral riboflavin supplementation (50 and
100 mg/day) on bacterial composition (diversity and quantity of anaerobic
microbiota) in comparison with placebo.
2. To determine the effects of 2 weeks oral riboflavin supplementation (50 and
100 mg/day) on the production of short chain fatty acids (SCFA) in faeces in
comparison with placebo.
3. To determine the effects of 2 weeks oral riboflavin supplementation (50 and
100 mg/day) on gastrointestinal (GI) comfort (bloating, flatulence) in
comparison with placebo using validated visual analogue scale (VAS)
questionnaires.
4. In a subgroup of participants, to determine the effects of 2 weeks oral
riboflavin supplementation (50 and 100 mg/day) on fasting and meal-stimulated
(75 g glucose, oral glucose tolerance test (oGTT)) secretion of the gut
peptides GLP-1, GLP-2 and PYY as well as on blood glucose, plasma insulin and
appetite feelings (using validated VAS questionnaires) in comparison with
placebo.
5. To determine the possible changes in stool characteristics such as faeces pH
and dry weight upon riboflavin supplementation.
6. To determine any possible effect on gut permeability, assessment of
permeability related biomarkers: I-FABP (plasma) and SM-22 (serum) upon
riboflavin supplementation.
7. To determine the effects of 2 weeks oral riboflavin supplementation on
riboflavin concentration in faeces and plasma.
Background summary
The correlation between nutrition and intestinal microbiota as well as the role
of the intestinal microbiota in human health and disease is well established.
Faecalibacterium prausnitzii is one of the most abundant bacteria in the human
gut which has anti-inflammatory properties and is one of the major producers of
the short chain fatty acid (SCFA) butyrate which serves as the main energy
source for intestinal epithelial cells. Decreased numbers of F. prausnitzii are
associated with inflammatory bowel diseases (IBD) such as e.g. Crohn*s disease.
In addition, Crohn*s disease patients have increased numbers of Adherent
Invasive Escherichia coli (AIEC) in their fecal and mucosal samples.
Studies comparing the gut microbiota between obese and lean individuals with or
without type-2-diabetes mellitus (T2DM) have revealed that patients with T2DM
also have reduced levels of F. prausnitzii4 suggesting that F. prausnitzii
might be involved in the regulation of glucose and energy homeostasis.
Alterations in the composition of the gut microbiome modulates fermentation
capacity and the secretion of SCFA of gut microbiome, which may be one of the
key signals of the gut to communicate with the brain to regulate blood glucose
and appetite (the gut-brain axis)5. Previous work indicates a role of the
microbiota and SCFA in regulating the release of hormones such as ghrelin,
GLP-1 and PYY from entero-endocrine cells. All of these hormones are known to
be pivotal in the regulation of glucose and energy homeostasis.
A pilot study with healthy volunteers showed that riboflavin (vitamin B2)
supplementation increases the numbers of F. prausnitzii and results in a higher
production of the beneficial SCFA, butyrate which has anti-inflammatory
properties and could be used as a primary energy source by epithelial cells.
Recent in vitro studies by our group have revealed that F. prausnitzii uses
riboflavin for extracellular electron transfer to shuttle electrons to oxygen,
unlike other butyrate producers, such as Roseburia.
In this trial we now aim to investigate comprehensively the effect of
riboflavin supplementation on the abundance of F. prausnitzii and on other
members of the gut microbiota in faeces of healthy volunteers. Additionally we
will assess whether riboflavin supplementation affects the abundance of
potentially pathogenic bacteria such as AIEC. Finally, we will evaluate the
effect of riboflavin supplementation on the production of SCFA and potential
changes in glucose and energy homeostasis.
Our hypothesis is that supplementation of the diet with riboflavin will result
in an increase in the amount of F. prausnitzii and other beneficial intestinal
microbiota with effects on the secretion of SCFA and subsequently glucose and
energy homeostasis.
Study objective
In this trial we now aim to investigate comprehensively the effect of
riboflavin supplementation on the abundance of F. prausnitzii and on other
members of the gut microbiota in faeces of healthy volunteers. Additionally we
will assess whether riboflavin supplementation affects the abundance of
potentially pathogenic bacteria such as AIEC. Finally, we will evaluate the
effect of riboflavin supplementation on the production of SCFA and potential
changes in glucose and energy homeostasis.
Study design
Randomized, placebo-controlled, double-blind, parallel-group trial.
Intervention
Each participant group (n=35) will receive one of three interventions:
- 50 mg riboflavin once per day for two weeks
- 100 mg riboflavin once per day for two weeks
- 0 mg riboflavin once per day (placebo) for two weeks
The intervention will be preceded by a 7 days run-in period (baseline) and 7
days of wash-out period will follow the intervention period.
Study burden and risks
This is a study with healthy volunteers. Participating in this study has a
potential health benefit. Previous pilot studies show that in healthy
participants, riboflavin supplementation increases the amount of the
beneficial F. prausnitzii, and results in a higher production of the
beneficial SCFA butyrate. In vitro studies revealed that unlike other
anaerobic bacteria, F. prausnitzii uses riboflavin for extracellular electron
transfer to shuttle electrons to oxygen and therefore tolerates limited amounts
of oxygen.
Usage of riboflavin is considered to be safe and burden free. Riboflavin is an
EU approved food supplement. It is freely available in tablet form in health
shops and supermarkets without a need for prescription. The riboflavin
supplement may give a harmless yellow discoloration of the urine few hours
after ingestion. This discoloration is temporary and there is no need to
discontinue the riboflavin supplementation.
Participants attend a screening at the start of the study in which they provide
small volumes of blood. Besides, there will be a total of 4 test days of 1,5-4
hours per participant. On THREE TEST DAYS participants will be required to
provide small volumes of blood and to complete short questionnaires. Prior to
test days they are asked to collect a stool sample. During blood-sampling there
is a small chance of bleeding at the puncture site, fainting or light skin
infection. The examination of the vital functions will be carried out by
trained research nurses and is not very stressful for participants. Mentioned
risks are rare if performed by qualified personnel at UMCG.
*
Wurmisweg 576
Kaiseraugst CH-4303
CH
Wurmisweg 576
Kaiseraugst CH-4303
CH
Listed location countries
Age
Inclusion criteria
Inclusion criteria:
1. Males or Females, age 20 - 60 years.
2. Participant is willing to stick to its normal habitual diet excluding consumption of any unusual high energy-rich or fat-rich meals or prolonged fasting, etc. throughout the study period.
3. Participant is willing to maintain its habitual physical activity patterns throughout the study period.
4. Participant has been stable in body-weight within the last 6 months.
5. Participant has no health conditions that would prevent him/her from fulfilling the study requirements as judged by the investigator on the basis of medical history and routine laboratory test results.
6. Participant has a body mass index (BMI) of >=18.5 and <= 24.9 kg/m2 at screening.
7. Participant is willing to refrain from consuming alcoholic drinks 24 h prior to test days (V2-V3).
8. Participant is not smoking.
9. Participant is able and motivated to comply with protocol requirements like for instance take the investigational product the way it is prescribed and to do the tests.
10. Participant understands the study procedures and signs forms providing informed consent to participate in the study.
Exclusion criteria
1. Participant has abnormal clinical chemistry and haematology laboratory test results of clinical significance that in the judgment of the investigator would interfere with the participant*s ability to comply with the study protocol (which might confound the interpretation of the study results), or put the participant at undue risk.
2. Participants with a history of GI disorders that are likely to interfere with the mode of action of the test product.
3. Participant has donated more than 300 mL of blood during the three months prior to screening.
4. Participant has a history, in the judgment of the investigator, of a psychological illness or condition such as to interfere with the participant*s ability to understand the requirements of the study.
5. Use of antibiotics or signs of active systemic infection in the last 6 months.
6. Participants who are on hypocaloric/hypercaloric diet aiming for weight loss/gain.
7. Participant has a history or presence of cancer in the prior two years, except for non-melanoma skin cancer.
8. Participant is pregnant, planning to be pregnant during the study period, lactating, or women of childbearing potential who are unwilling to commit to the use of a medically approved form of contraception throughout the study period. The method of contraception must be recorded in the source documentation.
9. Regular use of dietary supplements e.g. riboflavin, fish oil, 1 month prior study inclusion.
10. Participant has had exposure to any non-registered drug product within 30 days prior to the screening visit.
11. Recent history of (within 12 months of screening visit) or strong potential for alcohol or substance abuse. Alcohol abuse is defined as >60g (men) / 40g (women) pure alcohol per day (1.5 l / 1 l beer resp. 0.75 l / 0.5 l wine).
12. Participant has a known allergy or sensitivity to study product or any ingredients of the study product.
13. Use of commercially available probiotic, prebiotic and other supplements that may affect the gut microbiota
Design
Recruitment
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 | NL54701.042.15 |