A Trial to Evaluate the Effects of Bifidobacterium Longum NCC3001 on Intestinal and Psychological Symptoms in Subjects With Irritable Bowel Syndrome

Inclusion Criteria:

1. Male or female, age between 18 and 70 years inclusive.

2. Willing and able to sign written informed consent prior to study entry.

3. Able to comply with the study procedures, in the opinion of the investigator.

4. Subjects diagnosed with IBS. All subtypes based on Rome IV Criteria with active IBSsymptoms as indicated by a score of ≥ 125 on the IBS-SSS.

5. Subjects with psychological symptoms in the absence of a psychiatric diagnosis,defined as a score of 5 to 13 in the depression domain and/or a score of 4 to 9 inthe anxiety domain of the DASS-21 questionnaire.

Exclusion Criteria:

1. Concurrent formal diagnosis by a psychiatric specialist, including any mood oranxiety disorder, according to the diagnostic criteria of the Diagnostic andStatistical Manual of Mental Disorders 4th or 5th edition.

2. Concurrent systemic disease and/ or laboratory abnormalities considered by theinvestigator to be clinically relevant or that could interfere with data collectionor interpretation.

3. Concurrent organic gastrointestinal pathology other than benign polyps,diverticulosis, hemorrhoids, lipomas, and melanosis coli.

4. History of attempted suicide in the past 5 years.

5. Previous abdominal surgery except for hernia repair, appendectomy, caesariansection, tubal ligation, hysterectomy, and hemorrhoidectomy.

6. History of substance abuse in the past 2 years, including opiates, phencyclidine,benzodiazepines, amphetamines, cocaine, heroin, alcohol, and cannabinoids (except ifmedically indicated).

7. Subjects who are on daily treatment with therapeutic doses of drugs having centralnervous system effects, including antidepressants and/ or anxiolytics. Low doses of (I) tricyclic antidepressants for abdominal pain/diarrhea related to IBS and (II)anxiolytics used as sleeping pills will be permitted if dose is stable > 3 monthsprior to the date of randomization.

8. Pregnant or breastfeeding women.

9. Subjects with dementia or other cognitive impairment.

10. Subjects who received antibiotics within the 4 weeks prior to the date ofrandomization .

11. Known or suspected allergies to the study products.

12. Subjects with increased risk of probiotic sepsis as the following conditions: Immunecompromise, including debilitating state or malignancy, central venous catheter,impaired intestinal epithelial barrier (acute diarrheal illness, intestinalinflammation, etc.), cardiac valvular disease.

13. Subjects currently participating or having participated in a therapeutic trialwithin 3 months prior to the date of randomization.

14. Medically diagnosed lactose intolerance and fructose intolerance without being on astable lactose or fructose free diet (> 3 months prior to the date ofrandomization).

15. Medically diagnosed celiac disease.

16. Consumption of any probiotic supplements specified as containing Lactobacillus,Bifidobacteria, Streptococcus, Bacillus coagulans, and Saccharomyces at least 2weeks prior to the date of randomization.

17. Subjects on regular use of drugs to control IBS symptoms such as bile acid binders (cholestyramine, colestipol or colesevelam, rifaximin, alosetron, lubiprostone,eluxadoline and linaclotide).

18. Recently initiated exclusion diets. Subjects on stable exclusion diets (> 3 monthsprior to the date of randomization) will not be excluded. This includes subjectswith the following diets: gluten-free, lactose-free, paleo, vegetarian, vegan, andlow-carbohydrate.

19. Low-FODMAP diet. Subjects on the induction phase of the FODMAP exclusion will not beenrolled. Subjects on the maintenance phase of the diet for more than 3 months priorto the date of randomization with stable diet can be considered for enrollment.