BSCU1 and Immune Function

Study Overview
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Brief Summary
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The current study aims to explore a range of possible pathways by which BSCU1 could beneficially modulate the immune system, in three target populations representing the general population.

Detailed Description
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This exploratory study is designed as a single-arm study with repeated measures, involving three different populations, in which each subject serves as its own control. The duration of the intervention is 4 weeks, with biomarker assessments at baseline, after 2 weeks, and after 4 weeks intervention.

Official Title
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Change in Markers of Immune Function Associated With Bacillus Subtilis CU1 Intervention in Different Age Groups

Conditions
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General Population

Intervention / Treatment
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* Dietary Supplement: B. subtilis CU1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 30 ≤ age ≤ 49 years BMI ≥ 18.5 and ≤ 25 kg/m2 In good health as assessed during screening (by questionnaire), and the medical investigator's professional judgment Non-smoking Elderly 65 ≤ age ≤ 79 years BMI ≥ 22.0 and ≤ 28.0 kg/m2 Generally healthy as assessed during screening (by questionnaire), and the medical investigator's professional judgment Non-smoking Children 3 ≤ age ≤ 6 years Healthy BMI, cut-off points will be used as indicated by JGZ Generally healthy as assessed during screening (by parental anamnesis), and the study physician's professional judgment Exclusion Criteria: Adults and elderly Chronic illness (e.g., diabetes mellitus, cardiac insufficiency, respiratory insufficiency, cancer, chronic kidney or liver disease), Acute infection in the past month Gastrointestinal disorders (e.g., inflammatory bowel disease), Acute gastroenteritis in the past 2 months Any vaccination in the past month or any scheduled vaccination during the study period Treatment with antibiotics within 2 months before the start of the study and during the study period Regular use of laxative agents Immunodeficiency disorder Use of anti-inflammatory or immunosuppressive drugs (e.g.cyclosporine, azathioprine, systemic corticosteroids, antibodies) Unexplained weight loss or weight gain of > 3 kg in the 3 months prior to pre-study screening Regular consumption of probiotics within 1 month before start of the study Evidence of current excessive alcohol consumption (>4 consumptions/day or >20 consumptions/week) or drug (ab)use Mental status that is incompatible with the proper conduct of the study Children Acute respiratory or gastrointestinal infection in the past month Chronic illness (e.g. chronic infections, systemic or metabolic disease) Gastrointestinal disorders (e.g., inflammatory bowel disease), Acute gastroenteritis in the past 2 months Any vaccination in the past month or any scheduled vaccination during the study period Treatment with antibiotics within 2 months before the start of the study and during the study period Immunodeficiency disorder Use of anti-inflammatory or immunosuppressive drugs (e.g.cyclosporine, azathioprine, systemic corticosteroids, antibodies) Regular use of laxative agents Regular consumption of probiotics within 1 month before start of the study

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BSCU1<br>B. subtilis CU1 at 2 billion CFUs daily for 4 weeks | Dietary Supplement: B. subtilis CU1<br>* 2 billion CFUs daily, for 4 weeks<br>* Other names: B. subtilis CNCM I-2745;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal sIgA | Change in fecal sIgA concentration | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum cytokine concentration | Change in serum cytokines concentration (e.g. MIP-1α, IL-6, Il-10, IFN-γ, TNF-α, IL-1β) in elderly using a commercial Multiplex Bead Immunoassay (Bio-Rad, Veenendaal, The Netherlands) | 4 weeks | 
| Ex-vivo cytokines concentration | Change in control and Lipopolysaccharide (LPS) stimulated cytokine (e.g. MIP-1α, IL-6, Il-10, IFN-γ, TNF-α, IL-1β) production in whole blood in adults and elderly using a commercial Multiplex Bead Immunoassay (Bio-Rad, Veenendaal, The Netherlands) | 4 weeks | 
| Ex-vivo phagocytosis | Ex-vivo phagocytic function of monocytes and granulocytes using the commercial pHrodo, BioParticles phagocytosis assay kit (Invitrogen, ThermoFisher) for flow cytometry | 4 weeks | 
| Fecal microbiota | Fecal microbiota composition using shotgun metagenomics sequencing | 4 weeks | 
| RNA sequencing | Gene expression in PBMC (RNA sequencing) | 4 weeks | 
| Immune cell phenotyping | Immune cell phenotyping will be performed by labelling of the cell with cell specific markers and measured by means of flow cytometry. Two panels of each 8-12 markers will be used for general cell phenotyping, including activation markers, and T cell specific phenotyping in PBMCs. | 4 weeks |