To study effects of AXOS (1) on gut health including among other parameters intestinal transit time, fecal cytotoxicity, pH, inflammatory markers, short-chain fatty acids and microbiota composition), gut permeability and gut functioning (bloating,…
ID
Source
Brief title
Condition
- Gastrointestinal conditions NEC
- Metabolism disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Whole gut transit measured by clinically validated method with radio-opaque
marker. A capsule containing 10 radio-opaque markers is ingested for 6
consecutive days to distribute the markers evenly throughout the body. On day
seven, the radio-opaque markers are visible on fluoroscopy images and numbers
of retained markers are counted. Whole gut transit is determined by dividing
the number of retained markers by the daily dosage number.
Secondary outcome
Markers of gastrointestinal health:
* Fecal bulking, defecation frequency and stool consistency. This will be
measured by fecal weight and a questionnaire on gastro-intestinal symptoms,
including the severity and frequency of symptoms associated with intestinal
functioning such as bloating, rumbling, defecation frequency and the stool
consistency based on the Bristol stool chart
* Gastric emptying and oro-cecal transit time will be measured based on
13C-octanoic acid breath test and Inulin breath test, respectively. Determining
gastric emptying rate and oro-cecal transit is important to identify
differential effects on the upper or lower gastrointestinal transit
* in vivo* gut barrier function by means of a multi-sugar assay for
site-specific gastro-intestinal permeability analysis, to identify differential
effects in upper and lower gastrointestinal permeability
* Microbiota composition (16 r RNA gene sequencing, HITChip) and fecal SCFA
(LCMS) will provide insights in prebiotic-induced effect on microbiota
composition and activity
* fecal water cytotoxicity (CytoTox*ONE Homogeneous Membrane Integrity Assay)
fecal pH and inflammatory markers (e.g. calprotectin) are validated biomarkers
that define the gastrointestinal health status
Markers of metabolic health:
* Energy expenditure and substrate oxidation before and after a standardized
breakfast meal test (indirect calorimetry)
* Circulating Metabolites (glucose free fatty acids, triglycerides) and
hormones (insulin, GLP-1, PYY and angiopoietin-like 4 ANGPTL4) during fasting
and after the mixed high fat meal test
* Systemic Inflammatory markers like TNF-*, IL-6, IL-1, Lipopolysaccharide
binding protein (LBP)
* Body weight, BMI and body compositions ( bioimpedance)
* Adipose tissue gene and/or protein expression involved in functional pathways
is determined to detect a potential effect of microbiota modulation on adipose
function and substrate metabolism
Questionnaires:
* Questionnaires on quality of life and activity
Background summary
Dietary fibre intake provides many health benefits. A sufficient or generous
intake of dietary fibre reduces the risk for developing coronary heart disease,
stroke, hypertension, diabetes, obesity and certain gastro-intestinal
disorders. Increased consumption of dietary fibre has been shown to improve
serum lipid concentrations, reduced blood pressure, improve blood glucose
control in diabetes, promotes regularity, helps in losing weight and improves
immune function. The most pronounced effect of dietary fibers is on
gastrointestinal transit (GI) time and fecal bulking, attributed mostly to
insoluble, non-fermentable dietary fibers such as wheat bran. GI transit is an
important parameter of gut health relevant for many physiological and metabolic
processes. Other dietary fibers such as soluble and fermentable fibers function
as prebiotics, which are fermented in the colon and thus positively affect
microbiota composition and activity. However, little is known about effect of
prebiotic fibers on gastrointestinal transit and the metabolic consequences.
Additionally, potential shifts in the microbiome have not been evaluated at a
large scale with *state-of the art* metagenomic profiling techniques. In this
study, we investigate the effect of prebiotic fiber
arabinoxylan-oligosaccharides (AXOS) on gastrointestinal transit time and
markers of gut health and relate them to the metabolic parameters. Integrating
gut physiology and microbiome with host parameters of systemic inflammation,
glucose, lipid and energy metabolism would yield unique new insights that may
hold great relevance in the prevention of chronic metabolic diseases. This is
of particular relevance for the wheat bran derived arabinoxylans, which have
been reported to have a distinct effect on short chain fatty acid (SCFA)
production by the microbiota, and affect satiety and glycemic and insulinemic
profiles in the human host.
Hypothesis:
We hypothesize that the daily oral intake of AXOS might modify gastrointestinal
transit and microbiota composition and activity and that these factors (and
their interaction) are related to an improvement of gastrointestinal and
metabolic health
Study objective
To study effects of AXOS (1) on gut health including among other parameters
intestinal transit time, fecal cytotoxicity, pH, inflammatory markers,
short-chain fatty acids and microbiota composition), gut permeability and gut
functioning (bloating, rumbling, stool frequency, stool consistency (based on
the Bristol stool chart) and flatulence) (2) on systemic markers of host
metabolic and immune health including substrate and energy expenditure,
circulating metabolites, inflammatory and hormone profiles, adipose tissue
markers (3) to relate parameters of gut health and functioning and microbiota
composition to metabolic and immune health and quality of life (determined by
questionnaire)
Study design
Double-blind, placebo-controlled, randomized parallel design
Intervention
In this study there will be two different intervention groups:
1. Wheat-derived, Arabinoxylan-oligosaccharides (AXOS)
15g/day ingested with the meals (5 g in beverage, to be consumed three times a
day)
2. Placebo/control: maltodextrin
15g/day ingested with the meals (5 g in beverage, to be consumed three times a
day)
The duration of the intervention will be 12 weeks. The type of treatment will
be blinded for both the volunteers and the researchers.
Study burden and risks
All subjects will be screened before participation and thereby receive
information about their health status. The general interest of this study is to
study effect of wheat bran-derived dietary fibers on intestinal health and
functioning and metabolic health.
Burdens that volunteers can experience are the time spent with the study
(subjects will have to invest approximately 30 hours in the study,divided among
2 test days, 2 screening visit and 4 short visits and the dietary and healthy
regimen they have to follow. Also the collection of fecal samples can be
experienced as a burden, because they have to handle them themselves and have
to store them at home. Also the 12 week intake of the supplements can be seen
as a burden for the subjects.
During the test days, blood will be collected via a venous catheter.
Venapunctures can occasionally cause a local hematoma or a bruise. Some
participants report pain during venapuncture. During visit 1, 40 ml blood will
be taken. During visit 3 and 8 the total amount of blood sampled is 180 ml per
test day, totaling 400 ml during the whole test period. During visit 3 and 8,
an adipose tissue biopsy will be taken. The adipose tissue biopsy might cause
local hematoma as well. To minimize the risk for a hematoma, the biopsy place
will be compressed for approximately 10 minutes after biopsy. The place of
incision will leave a small scar (3 mm for adipose tissue biopsy). To promote
good wound healing, the incision will be sealed with sterile steristrips and a
waterproof band-aid.
Koningsplein 59G
Maastricht 6224EG
NL
Koningsplein 59G
Maastricht 6224EG
NL
Listed location countries
Age
Inclusion criteria
- Healthy, normal/overweight men and women (BMI * 20 kg/m2 <30kg/m2)
- Aged 20-55 years
- Caucasian
- Normal fasting glucose (<6.1 mmol/L.)
- Normal blood pressure (systolic blood pressure 100-140 mmHg, diastolic blood pressure 60-90 mmHg)
- Weight stable in last 3 months (±2 kg)
- A low defecation frequency, <4 times/week and no constipation or underlying pathology
- A slow gastro-intestinal transit (> 50th percentile based on Sadik et al. 2003, 2004)
Exclusion criteria
- Woman lactating, pregnant or (post)-menopausal
- Regular smokers
- People with intensive fitness training, eg. athletes (*3 per week * 1 hour training)
- Diabetes Mellitus (defined as FPG * 7.0 mmol/l and or 2h PG * 11.1 mmol/l)
- Gastro-intestinal diseases or abdominal surgery, cardiovascular diseases, cancer, liver or kidney malfunctioning, disease with a life expectation shorter than 5 years.
- Following a hypocaloric diet
- Gluten intolerance
- Regular use of laxation products, or use of antibiotics, probiotics or prebiotics 3 months prior to the start of the study
- Current use of medication interfering with study intervention or interfering with study endpoints/hypotheses
- Not to be able to understand the study information
- Blood donation 2 months prior to the study and during the study
- Participation in other studies
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL52300.068.15 |
| Other | study has been registered |
| OMON | NL-OMON23115 |