Impact of Whole Grain Rye Bread on Modulating Microbiota-gut-brain Axis in Healthy Subjects
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Microbiota composition baseline vs after intervention using 16S RNA gene sequencing
Study Overview
Brief Summary
This randomized controlled trial aims to study how a high intake of a fibre-rich bread affects the composition and functioning of the gut microbiota in healthy subjects, and how this, in turn, impacts on the release of gut peptides, intestinal permeability, stress and cognitive performance.
Detailed Description
Healthy subjects will be recruited for a 3-week, randomized, parallel-controlled study. Subjects that are eligible to take part in the study will be blinded and randomly allocated to consume a fibre-rich bread or a control bread daily for 3 weeks. Measurements of biomarkers related to the gut-brain axis, microbiota composition and functioning, intestinal permeability, stress and cognitive functioning will be conducted on two separate test days, at baseline and after the 3 weeks intervention. On both test days (day 0 and day 21) subjects will come to the study centre after a 10 hours overnight fast and will deliver faecal samples collected at home. At the study centre, blood samples will be collected and a device for continuous assessment of autonomic nervous system response (Biopac) will be placed. Subjects will drink a multisugar solution and urine samples will be collected for gut permeability analysis. Sugar solution intake will be followed by a baseline period during which participants will rest for 30 minutes to adapt to the laboratory setting. After the baseline period, subjects will conduct a stress test and cognitive tests. Visual analogue scales (VAS) to assess momentary perceived stress levels and saliva samples will be collected before and after the stress test. The study subjects will also complete questionnaires at both visits (food frequency questionnaire, food diary, physical activity, gastrointestinal symptom rating scale, Euro Quality of Life).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Masking Description
double blinding
Eligibility Criteria
- Ages
- 18 Years to 44 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age 18-44 years
- •Body mass index (BMI) 18,5-30 kg/m2 (normal weight or overweight)
Exclusion Criteria
- •Significant acute or chronic illness, including an inflammatory or a functional disease of gastrointestinal track and psychiatric and psychological disorders
- •Anxiety or depression (according to Hospital Anxiety and Depression Scale (HADS score) and Depression Anxiety Stress Scale (DASS-21 score))
- •Use of a medication that may interfere with the study (e.g. cannabis, antipsychotics, anxiolytics, antidepressants, proton-pump inhibitors)
- •Abuse of alcohol or drugs (according to AUDIT score)
- •Use of antibiotic medication within the past 3 months before the study
- •Use of laxative or anti-diarrhoea medication within the past 3 months before the study
- •Regular consumption of probiotic or prebiotic product for the past 6 weeks before the study
- •A diet that may interfere with the study (such as gluten free or low-carb diet)
- •Pregnancy or breastfeeding
- •Premenopausal female with irregular or short menstruation cycle and not using hormonal contraception
- •Colour blindness, dyslexia or dyscalculia
- •Unable to absent from caffeine, alcohol or intense exercise for 12 hours prior measurements.
Outcomes
Primary Outcomes
Microbiota composition baseline vs after intervention using 16S RNA gene sequencing
Time Frame: faecal samples collected before and after intake of bread for 3 weeks
Difference in gut microbiota composition in faecal samples before (baseline) and after intake of six slices of bread for 3 weeks (after intervention) using 16S RNA gene sequencing
Secondary Outcomes
- Concentrations of blood neuroactive peptide Y (NPY)(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood glucagon like peptide-2 (GLP-2)(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood brain-derived neurotrophic factor (BDNF)(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood alkylresorcinols(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood lipopolysaccharide-binding protein (LBP)(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood soluble CD-14 (sCD-14)(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of circulatory short-chain fatty acids SCFA(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of faecal SCFA(faecal samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood glucagon like peptide-1 (GLP-1)(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood gastric inhibitory polypeptide (GIP)(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood cytokines(blood samples collected before and after intake of bread for 3 weeks)
- Microbiota composition whole grain rye bread vs control bread using 16S RNA gene sequencing(faecal samples collected before and after intake of bread for 3 weeks)
- Concentrations of blood peptide YY (PYY)(blood samples collected before and after intake of bread for 3 weeks)
- Concentrations of sugars in urine(urine samples collected before and after intake of bread for 3 weeks)
- Concentrations of saliva cortisol during stress test(Saliva samples collected before the stress test, after the introduction phase, directly after the acute stress phase, 5 minutes, 10-15 minutes, 60 minutes, and 75 minutes after the stress test)
- Concentrations of saliva alpha-amylase during stress test(Saliva samples collected before the stress test, after the introduction phase, directly after the acute stress phase, 5 minutes, 10-15 minutes, 60 minutes, and 75 minutes after the stress test)