The Effect of Two Probiotic Products on the Intestinal Barrier Function in Patients With Irritable Bowel Syndrome

Study Overview
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Brief Summary
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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
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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).

Official Title
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The Effect of Two Probiotic Products on the Intestinal Barrier Function in Patients With Irritable Bowel Syndrome

Conditions
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IBS

Intervention / Treatment
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* Dietary Supplement: Probiotics
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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: Known organic gastrointestinal disease (e.g. inflammatory bowel disease, IBD) Previous abdominal surgery which might influence gastrointestinal function, except appendectomy and cholecystectomy History of or present gastrointestinal malignancy or polyposis Recently (within the last 6 months) diagnosed gastrointestinal infection Current diagnosis of dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis) Autoimmune disease and/or patients receiving immunosuppressive medications Chronic pain syndromes (e.g. fibromyalgia) Chronic fatigue syndrome Severe endometriosis Coeliac disease Recently (within the last 3 months) diagnosed lactose intolerance Females who are pregnant or breast-feeding 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 Recent (< 4 weeks) intake of proton pump inhibitors, PPIs (e.g., omeprazol) Use of anti-depressants in the last 3 months 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 Antimicrobial treatment 6 weeks prior to first screening visit Antimicrobial prophylaxis (eg. acne, urinary tract infection) Regular consumption of probiotic products 4 weeks prior to first baseline visit 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. Inability to maintain exercise routine and dietary pattern during the study. Abuse of alcohol or drugs Any clinically significant present or past disease/condition which in the investigator's opinion could interfere with the results of the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactobacillus reuteri strain 1<br>Probiotic compound | Dietary Supplement: Probiotics<br>* 5x10^8 colony forming units (CFU) of each probiotic strain, two capsules per day over six weeks<br>|
| Experimental: Lactobacillus reuteri strain 2<br>Probiotic compound | Dietary Supplement: Probiotics<br>* 5x10^8 colony forming units (CFU) of each probiotic strain, two capsules per day over six weeks<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Similar in shape and taste to intervention capsules but without the probiotic components, two capsules per day over six weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in small intestinal permeability after 6 weeks (urinary lactulose/rhamnose ratio, 0-5h) | 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 | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in small intestinal permeability after 3 weeks (urinary lactulose/rhamnose ratio, 0-5h) | 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 | 3 weeks | 
| Change in whole gut permeability after 6 weeks (urinary sucralose/erythritol ratio, 0-24h) | Difference between intervention with the probiotic products compared to the placebo in whole gut permeability, measured as urinary sucralose/erythritol excretion ratio (0-24hrs) | 6 weeks | 
| Change in whole gut permeability after 3 weeks (urinary sucralose/erythritol excretion ratio, 0-24h) | Difference between intervention with the probiotic products compared to the placebo in whole gut permeability, measured as urinary sucralose/erythritol excretion ratio (0-24hrs) | 3 weeks | 
| Change in colonic permeability after 6 weeks (urinary sucralose/erythritol ratio, 5-24h) | Difference between intervention with the probiotic products compared to the placebo in colonic permeability, measured as urinary sucralose/erythritol ratio (5-24hrs) | 6 weeks | 
| Change in colonic permeability after 3 weeks (urinary sucralose/erythritol ratio, 5-24hrs) | Difference between intervention with the probiotic products compared to the placebo in colonic permeability, measured as urinary sucralose/erythritol ratio (5-24hrs) | 3 weeks | 
| Change in gastroduodenal permeability after 6 weeks (urinary sucrose excretion, 0-5hrs) | Difference between intervention with the probiotic products compared to the placebo in gastroduodenal permeability, measured as urinary sucrose excretion (0-5hrs) | 6 weeks | 
| Change in gastroduodenal permeability after 3 weeks (urinary sucrose excretion, 0-5hrs) | Difference between intervention with the probiotic products compared to the placebo in gastroduodenal permeability, measured as urinary sucrose excretion (0-5hrs) | 3 weeks | 
| Change in inflammatory status after 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) | 3 weeks | 
| Change in inflammatory status after 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) | 6 weeks |