IBS
Conditions
Brief summary
This study will investigate the effects of supplementation with two different probiotic products (Lactobacillus reuteri strains) on the intestinal barrier function, gut health and stress symptoms in diarrhoea-predominant irritable bowel syndrome (IBS-D) patients.
Detailed description
After having given their written informed consent, subjects will complete screening procedures to evaluate their eligibility for the study (visit 1). Study participants will undergo two baseline visits (visits 2 and 3, 3 weeks apart) to account for individual variations, and will then be randomly assigned to 6-week intake of one of two Lactobacillus reuteri strains, or placebo in a ratio of 1:1:1 (stratified by sex). Participants will attend a study visit three weeks into the intervention (visit 4) and at the end of the intervention (visit 5, week 6). The intestinal permeability will be assessed using a standardized multi-sugar test at visit 2, visit 3, visit 4, and at end of intervention (visit 5). Blood, saliva and faecal samples will be collected at visit 2-5. In addition, gastrointestinal symptoms will be recorded at those visits (using Gastrointestinal symptom rating scale-IBS, GSRS-IBS; IBS severity scoring system, IBS- SSS). Quality of life using the 5Q-5D-5L and Hospital Anxiety and Depression Scale (HADS) scores will also be recorded at those visits. In addition, at visit 3 and visit 5, the IBS-Quality of life (IBS-QoL) and the Perceived Stress Scale (PSS) will be completed. In a daily diary, participants will record stool frequency and consistency from visit 2 until end-of-study visit 5. Dietary habits of the patients will be assessed via a food frequency questionnaire (FFQ) and a 3-day food diary before the intervention (between visit 2 and 3).
Interventions
DIETARY_SUPPLEMENTProbiotics
5x10\^8 colony forming units (CFU) of each probiotic strain, two capsules per day over six weeks
OTHERPlacebo
Similar in shape and taste to intervention capsules but without the probiotic components, two capsules per day over six weeks
Sponsors
Örebro University, Sweden
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Fulfilled Rome IV diagnostic criteria for IBS with predominant diarrhoea * Mild-to-severe IBS symptoms according to the IBS severity scoring system (IBS-SSS; a score of ≥75) * Age: 18-65 years
Exclusion criteria
1. Known organic gastrointestinal disease (e.g. inflammatory bowel disease, IBD) 2. Previous abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy 3. History of or present gastrointestinal malignancy or polyposis 4. Recently (within the last 6 months) diagnosed gastrointestinal infection 5. Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation 6. Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis) 7. Autoimmune disease and/or patients receiving immunosuppressive medications 8. Chronic pain syndromes (e.g. fibromyalgia) 9. Chronic fatigue syndrome 10. Severe endometriosis 11. Coeliac disease 12. Recently (within the last 3 months) diagnosed lactose intolerance 13. Females who are pregnant or breast-feeding 14. Regular intake of systemic corticosteroids and anti-inflammatory medication (including non-steroidal anti-inflammatory drugs, NSAIDs) during the last 3 months or incidental use in the last 2 weeks prior to randomisation 15. Recent (\< 4 weeks) intake of proton pump inhibitors, PPIs (e.g., omeprazol) 16. Use of anti-depressants in the last 3 months 17. Regular oral intake of mast cell stabilising drugs (e.g. sodium cromoglycate) during the last 3 months or incidental use in the last 2 weeks prior to screening 18. Antimicrobial treatment 6 weeks prior to first screening visit 19. Antimicrobial prophylaxis (eg. acne, urinary tract infection) 20. Regular consumption of probiotic products 4 weeks prior to first baseline visit 21. Concurrent or recent (\<4 weeks) use of nutritional supplements or herb products affecting intestinal function (e.g. aloe vera, St. John´s Wort, fibres, prebiotics) if the investigator considers those could affect the study outcome. 22. Inability to maintain exercise routine and dietary pattern during the study. 23. Abuse of alcohol or drugs 24. Any clinically significant present or past disease/condition which in the investigator's opinion could interfere with the results of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in small intestinal permeability after 6 weeks (urinary lactulose/rhamnose ratio, 0-5h) | 6 weeks | Difference in small intestinal permeability, measured as the urinary lactulose/rhamnose secretion ratio (0-5h), after a 6-week intervention with the probiotic products compared to the placebo product |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in colonic permeability after 3 weeks (urinary sucralose/erythritol ratio, 5-24hrs) | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in colonic permeability, measured as urinary sucralose/erythritol ratio (5-24hrs) |
| Change in small intestinal permeability after 3 weeks (urinary lactulose/rhamnose ratio, 0-5h) | 3 weeks | Difference in small intestinal permeability, measured as the urinary lactulose/rhamnose secretion ratio (0-5h), after a 3-week intervention with the probiotic products compared to the placebo product |
| Change in whole gut permeability after 6 weeks (urinary sucralose/erythritol ratio, 0-24h) | 6 weeks | Difference between intervention with the probiotic products compared to the placebo in whole gut permeability, measured as urinary sucralose/erythritol excretion ratio (0-24hrs) |
| Change in whole gut permeability after 3 weeks (urinary sucralose/erythritol excretion ratio, 0-24h) | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in whole gut permeability, measured as urinary sucralose/erythritol excretion ratio (0-24hrs) |
| Change in colonic permeability after 6 weeks (urinary sucralose/erythritol ratio, 5-24h) | 6 weeks | Difference between intervention with the probiotic products compared to the placebo in colonic permeability, measured as urinary sucralose/erythritol ratio (5-24hrs) |
| Change in gastroduodenal permeability after 6 weeks (urinary sucrose excretion, 0-5hrs) | 6 weeks | Difference between intervention with the probiotic products compared to the placebo in gastroduodenal permeability, measured as urinary sucrose excretion (0-5hrs) |
| Change in gastroduodenal permeability after 3 weeks (urinary sucrose excretion, 0-5hrs) | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in gastroduodenal permeability, measured as urinary sucrose excretion (0-5hrs) |
| Change in inflammatory status after 3 weeks | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in inflammatory markers in blood (e.g. high-sensitive C-reactive protein) |
| Change in inflammatory status after 6 weeks | 6 weeks | Difference between intervention with the probiotic products compared to the placebo in inflammatory markers in blood (e.g. high-sensitive C-reactive protein) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in stool frequency and consistency (daily diary on bowel movement using Bristol Stool Chart) | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in stool frequency and consistency |
| Change in gastrointestinal symptoms measured by the IBS-specific gastrointestinal symptom rating scale (GSRS-IBS) | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in gastrointestinal symptoms (GSRS-IBS total score range 0-3, 0-no symptoms, 3-extreme degree of symptoms) |
| Change in gastrointestinal symptoms measured by the IBS symptom severity score (IBS-SSS) | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in gastrointestinal symptoms (IBS-SSS, total score range 0-500, 0-no symptoms, 500-extreme degree of symptoms) |
| Change in quality of life measured by IBS-specific quality of life (IBS-QOL) questionnaire | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in quality of life (IBS-QOL total range, range: 0-100, 0-low quality of life, 100-high quality of life) |
| Change in perceived stress using the perceived stress scale (PSS) | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in perceived stress (PSS range 0-40: 0-no stress, 40-high stress) |
| Change in anxiety and depression symptoms using the Hospital Anxiety and Depression Scale (HADS) | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in anxiety and depression symptoms (HADS range: 0 to 21 for anxiety and 0 to 21 for depression, 0-low levels, 21 high levels) |
| Change in salivary cortisol levels | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in salivary cortisol levels |
| Change in intestinal microbiota composition (16S rRNA-based next generation sequencing of faecal samples) after probiotic intervention | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in intestinal microbiota composition |
| Change in metabolomic profile in faecal samples after probiotic intervention | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples |
| Change in metabolomic profile in blood samples after probiotic intervention | 3 weeks | Difference between intervention with the probiotic products compared to the placebo in metabolomic profile in faecal samples |
Countries
Sweden
Outcome results
None listed