Clinical trial NCT06333717: Impact of Whole Grain Rye Bread on Health
Official title: Impact of Whole Grain Rye Bread on Modulating Microbiota-gut-brain Axis in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Diet
Keywords: dietary fibre
microbiota
gut-brain axis
Lead sponsor: Örebro University, Sweden
Sponsor class: OTHER
First posted: 2024-03-27
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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)
* Smoking
* 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.

Primary outcomes:
measure: Microbiota composition baseline vs after intervention using 16S RNA gene sequencing
timeFrame: faecal samples collected before and after intake of bread for 3 weeks
Secondary outcomes:
measure: Microbiota composition whole grain rye bread vs control bread using 16S RNA gene sequencing
timeFrame: faecal samples collected before and after intake of bread for 3 weeks
measure: Concentrations of circulatory short-chain fatty acids SCFA
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of faecal SCFA
timeFrame: faecal samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood glucagon like peptide-1 (GLP-1)
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood glucagon like peptide-2 (GLP-2)
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood peptide YY (PYY)
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood gastric inhibitory polypeptide (GIP)
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood neuroactive peptide Y (NPY)
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood brain-derived neurotrophic factor (BDNF)
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood cytokines
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood alkylresorcinols
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood lipopolysaccharide-binding protein (LBP)
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of blood soluble CD-14 (sCD-14)
timeFrame: blood samples collected before and after intake of bread for 3 weeks
measure: Concentrations of sugars in urine
timeFrame: urine samples collected before and after intake of bread for 3 weeks
measure: Concentrations of saliva cortisol during stress test
timeFrame: 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
measure: Concentrations of saliva alpha-amylase during stress test
timeFrame: 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
Other outcomes:
measure: Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale in Irritable Bowel Syndrome (GSRS-IBS)
timeFrame: 3 weeks
measure: Food habits measured by an electronic food frequency questionnaire Mealq
timeFrame: 3 weeks
measure: Food habits measured by a Food diary
timeFrame: 3 days
measure: Physical activity measured by the International Physical Activity Questionnaire (IPAQ)
timeFrame: 3 days
measure: Quality of life measured by the Euro Quality of Life questionnaire
timeFrame: once before and after intake of bread for 3 weeks
measure: Perceived stress measured by a Visual analog scale questionnaire
timeFrame: 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
measure: Cognitive control using Eriksen flanker task (Flanker task)
timeFrame: once before and after intake of bread for 3 weeks
measure: Working memory performance using a modified N-back task combined with recent-probes item-recognition task (Sternberg task)
timeFrame: once before and after intake of bread for 3 weeks
measure: Electrocardiogram (ECG) using the Biopac system
timeFrame: once before and after intake of bread for 3 weeks
measure: Electrodermal activity (EDA) using the Biopac system
timeFrame: once before and after intake of bread for 3 weeks
Locations:
city: Örebro
country: Sweden
facility: Örebro University
Study officials:
affiliation: Örebro University, Sweden
name: Rebecca Wall, PhD
role: PRINCIPAL_INVESTIGATOR
References: