Probiotics are live microbes that, when administered in adequate amounts, confer a health benefit. Examples of probiotic health benefits include the support of gastrointestinal (GI) health and immune health. Common probiotic strains include species from the Bacillaceae family (e.g. Bacillus genus) and Lactobacillaceae family of the Bacillota phylum (formerly Firmicutes), and species from the Bifidobacterium genus of the Actinomycetota phylum (formerly Actinobacteria). Bacillaceae species are particularly advantageous for oral probiotic applications because they can be manufactured as spores with highly proteinaceous coats that persist without refrigeration and resist the acidic and high bile salt conditions that occur across the human GI tract. The objective of this clinical study is to investigate the effects of daily oral supplementation with a novel Bacillus sp. spore preparation for 8 weeks on GI symptoms, intestinal barrier integrity, and fecal microbiome properties.
This will be a randomized, parallel, double-blind, placebo-controlled study consisting of one screening visit (Visit 1, Day -7) and four study visits (Days 0, 1, 57, and 58). At Visit 1 (Day -7), participants will arrive at the clinic in a fasting state (≥ 10 hours). After participants provide voluntary informed consent, participants 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 body mass index (BMI) will be calculated. Blood samples will be collected for chemistry, hematology, C-reactive protein (CRP), and insulin analyses. Participants will be dispensed a daily paper Gastrointestinal Tolerance Questionnaire (GITQ) with instructions to capture events occurring during the seven continuous days prior to Visit 2 (Day 0). The paper GITQ contains a series of questions regarding the presence and severity of GI symptoms occurring during the past 24 hours. Therefore, participants will be instructed to complete their first GITQ on the morning of Day -6 and the final GITQ on the morning of Day 0, just before their Visit 2. Additionally, a stool sample collection kit will be dispensed with instructions to a collect stool sample from a single bowel movement (for fecal microbiome analyses) within the 3 days immediately before Visit 2 (Day 0).
At Visit 2 (Day 0), participants will arrive at the clinic in a fasting state (≥ 10 hours). Participants will undergo clinic visit procedures (concomitant medication/supplement use, assess inclusion/exclusion criteria, body weight, and vital signs measurements) and adverse event (AE) assessment. Fecal samples will be collected, and subjects will be administered a 7-day recall GITQ. Participants will then undergo an intestinal permeability test where they will ingest four sugar probes (1 g mannitol, 1 g sucralose, 1 g erythritol, and 5 g lactulose) in approximately 240 mL water. Participants will be dispensed 2 separate containers to collect all urine over the following 24 hours, with urine collected from 0 to 5 hours in one container and from 5 to 24 hours in the second container. Participants will be instructed to return both containers to the clinic the following day at Visit 3 (Day 1). Upon completion of the GI permeability test, participants will be randomly assigned to a study product sequence. Participants will receive an email link for an electronic 7-day recall GITQ to be completed on Days 8, 15, 22, 29, 36, 43, 50, and 57. Participants will also receive information regarding daily links that will be sent via email to complete electronic 24-hour recall GITQs and will be instructed to complete these electronic 24-hour GITQs daily starting on day 51, which will be 6 days ahead of Visit 4. Participants will continue recording the 24-hour GITQ recall every day for seven total days (Days 51, 52, 53, 54, 55, 56, and 57). Additionally, a stool sample collection kit will be dispensed with instructions to collect a stool sample from a single bowel movement for fecal microbiome analyses within the 3 days immediately before Visit 4 (Day 57). In addition, a subset of male subjects will be selected to collect an additional fecal sample for fecal metabolomic and/or targeted analyte analyses.
At Visit 3 (Day 1), participants will return the 24-hour urine sample collection containers and undergo AE assessments. Participants will be dispensed their assigned study product and will be instructed to consume it once a day (1 capsule/d) with their meal that is typically the largest of the day for 56 days starting on Day 1.
At Visit 4 (Day 57), participants will arrive at the clinic fasted (≥ 10 hours) and undergo clinic visit procedures, including: concomitant medication/supplement use, review inclusion/exclusion criteria, body weight and vital signs measurements, and AE assessment. Fecal samples will be collected. Blood samples will be collected for chemistry, hematology, CRP, and insulin analyses. Participants will then complete the intestinal permeability test with the same procedures and study instructions described at Visit 2.
At Visit 5 (Day 58), participants will return the 24-hour urine sample collection containers and undergo AE assessments.
