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.

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).

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

No individual participant data will be shared, only data on group level will