Effect of Bacillus Subtilis BS50 Supplementation on Gastrointestinal Symptoms in Healthy Adults

Study Overview
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Brief Summary
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The primary objective of this study is to investigate the effect of a novel Bacillus subtilis spore preparation on abdominal bloating, flatulence, and burping in healthy adults.

Detailed Description
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Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Examples of probiotic health benefits include the support of gastrointestinal health, immune health, and mood. Common probiotic strains include species from the genera Lactobacillus, Bifidobacterium, and Bacillus. Bacillus species are particularly well suited for probiotic applications because they are often manufactured as spores that persist without refrigeration and show survivability in the acidic conditions of the human gut. BIO-CAT Microbials' proprietary Bacillus subtilis BS50 strain (BS50) has previously been shown in bacterial culture to secrete digestive enzymes and candidate gut microbiota-modulating molecules which may help support digestion and gastrointestinal health (unpublished data). BS50 also showed robust heat resistance and pH tolerance, which predicts strain survival across the wide pH range of the human gut. The objective of this clinical study is to investigate the effect of BS50 supplementation at 2x10⁹ CFU per day for 42 days on abdominal bloating, flatulence, and burping in healthy adults. This study will be a randomized, placebo-controlled, parallel design trial consisting of one screening visit (Visit 1) and two study visits (Visits 2 and 3). At Visit 1 (Day -7), subjects will arrive at the clinic in a fasting state. After subjects provide voluntary informed consent, subjects will undergo medical history, prior and current medication/supplement use, and inclusion and exclusion criteria assessments. Additionally, height, body weight, and vital signs will be measured and BMI will be calculated. Blood samples will be collected for chemistry and hematology analyses. Subjects will also be dispensed a paper Bowel Habits Diary with Bristol Stool Scale (BHD-BSS) and paper Gastrointestinal Tolerance Questionnaire (GITQ) with instructions to capture events occurring during the 7 continuous days prior to Visit 2 (Day 0). The GITQ contains a series of questions regarding the presence and severity of GI symptoms occurring during the past 24 h. At Visit 2 (Day 0), subjects will arrive at the clinic in a fasting state. Subjects will undergo clinic visit procedures (concomitant medication/supplement use, assess inclusion/exclusion criteria, body weight and vital signs measurements), and adverse event (AE) assessment. The paper BHD-BSS and GITQ will be collected and reviewed. To assess sleep quality and determine presence and duration of respiratory infection, subjects will be instructed to complete a paper Sleep Quality and Respiratory Infection Questionnaire (SQ-RIQ) in the clinic. Blood samples will be collected for assessment of markers of intestinal permeability, inflammation, and lipid profile. Subjects will be randomly assigned to a study product. Subjects will be dispensed their assigned study product and will be instructed to consume it once a day (1 capsule/d) for 42 days starting on Day 0. To assess sleep quality and determine presence and duration of respiratory infection, subjects will be dispensed a weekly electronic SQ-RIQ with instructions to complete this questionnaire weekly prior to Visit 3 (Day 42). Subjects will be dispensed the electronic BHD-BSS and electronic GITQ with instructions to capture events occurring daily leading up to Visit 3 (Day 42). At Visit 3 (Day 42), subjects will arrive at the clinic fasted and undergo clinic visit procedures (concomitant medication/supplement use, assess inclusion/exclusion criteria, body weight and vital signs measurements), and adverse event (AE) assessment. Blood samples will be collected for chemistry and hematology analyses as well as for assessment of markers of intestinal permeability, inflammation, and lipid profile.

Official Title
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A Randomized, Parallel, Double-blind, Placebo-Controlled Study to Investigate the Effect of a Bacillus Subtilis BS50 Spore Preparation on Gastrointestinal Symptoms in Healthy Adults

Conditions
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Gastrointestinal Health, Immune Health, Cardiovascular Health, Digestive Health

Intervention / Treatment
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* Dietary Supplement: Bacillus subtilis BS50 spore preparation
* Dietary Supplement: Maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 30-65 years of age, inclusive at Visit 1. BMI of 18.0 to 31.9 kg/m², inclusive, at Visit 1. Have ≥3 weekly total symptom score obtained by combining ratings for abdominal bloating, flatulence, and burping from the GITQ. Consumes a typical American diet. Exclusion Criteria: Abnormal laboratory test results of clinical significance at Visit 1. Clinically important GI condition that would potentially interfere with the evaluation of the study product. Recent (within 2 weeks of Visit 1) history of an episode of acute GI illness such as nausea/vomiting or diarrhea. Self-reported history (within 6 weeks of Visit 1) of constipation or diarrhea. Uncontrolled and/or clinically important pulmonary (including uncontrolled asthma), cardiac (including, but not limited to, atherosclerotic disease, history of myocardial infarction, peripheral arterial disease, stroke), hepatic, renal, endocrine (including Type 1 and Type 2 diabetes mellitus), hematologic, immunologic, neurologic (such as Alzheimer's or Parkinson's disease), psychiatric (including depression and/or anxiety disorders) or biliary disorders. Uncontrolled hypertension as defined by the blood pressure measured at Visit 1. Have received a COVID vaccine within 2 weeks of Visit 2 or expected to receive a COVID vaccine during the study period. Had a positive SARS-CoV-2 test and experienced symptoms for >2 months. History or presence of cancer in the prior 2 years, except for non-melanoma skin cancer. Weight loss or gain >4.5 kg in the 3 months prior to Visit 1. Antibiotic use within 3 months of Visit 1 and throughout the study period. Use of steroids within 1 month of Visit 1 and throughout the study period. Chronic use (i.e., daily on a regular basis) of anti-inflammatory medications (e.g., NSAIDS) within 1 month of Visit 1. Use of medications (over-the-counter or prescription) and/or dietary supplements, known to influence GI function.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bacillus subtilis BS50<br>Subjects will consume 1 capsule containing 2x10⁹ CFU of a Bacillus subtilis BS50 spore preparation once daily for 42 days. | Dietary Supplement: Bacillus subtilis BS50 spore preparation<br>* Subjects will consume 1 capsule containing 2x10⁹ CFU of a Bacillus subtilis BS50 spore preparation once daily for 42 days.<br>|
| Placebo Comparator: Placebo<br>Subjects will consume 1 capsule containing maltodextrin once daily for 42 days. | Dietary Supplement: Maltodextrin<br>* Subjects will consume 1 capsule containing maltodextrin once daily for 42 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abdominal bloating, flatulence, and/or burping | Daily, 8-item Gastrointestinal Tolerance Questionnaire | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite score of GI symptoms | Abdominal bloating, flatulence, burping, nausea, vomiting, abdominal cramping, stomach rumbling, and reflux (Gastrointestinal Tolerance Questionnaire) | 6 weeks | 
| Individual GI symptoms scores other than abdominal bloating, flatulence, and burping | Nausea, vomiting, abdominal cramping, stomach rumbling, and reflux (Gastrointestinal Tolerance Questionnaire) | 6 weeks | 
| Bowel function | Stool frequency, stool consistency, straining and discomfort during bowel movement, sensation of incomplete evacuation (Bowel Habits Diary with Bristol Stool Scale) | 6 weeks | 
| Biomarkers of gut permeability | Blood levels of zonulin, occludin, and lipopolysaccharide binding protein | 6 weeks | 
| Biomarkers of immune health | Blood levels of C-reactive protein, IL-8, IL-6, IL-10, IFN-γ, and TNF-α | 6 weeks | 
| Blood lipid profiling | Blood levels of triglyceride, total cholesterol (total-C), LDL-C, and HDL-C | 6 weeks | 
| Incidence and duration of cold/flu/respiratory infection | Weekly Sleep Quality and Respiratory Infection Questionnaire | 6 weeks | 
| Sleep quality | Weekly Sleep Quality and Respiratory Infection Questionnaire | 6 weeks | 
| Safety - Adverse Events | Self-reported adverse events at Visits 2 and 3 | 7 weeks | 
| Safety - Blood Chemistry Profile | Albumin, alkaline phosphatase, total bilirubin, calcium, chloride, creatinine, blood urea nitrogen, potassium, aspartate, aminotransferase, alanine aminotransferase, sodium, total protein, carbon dioxide, osmolality, and glucose | 7 weeks | 
| Safety - Blood Hematology Profile | White blood cell count, red blood cell count, hemoglobin concentration, hematocrit (as volume percent), mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelet counts | 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotic, Bacillus, subtilis, bloating