The Effects of a Novel Probiotic on Gastrointestinal Health in Generally Healthy Adults
Condition: Gastrointestinal Health; Immune Health; Digestive Health
Study type: Interventional

Summary: 
      The primary objective of this study is to investigate the effect of an oral probiotic
      (Bacillus sp. spore preparation) on abdominal bloating, flatulence, and burping in generally
      healthy adults. Secondary outcomes include intestinal barrier integrity and fecal microbiome
      properties (taxonomical structure, diversity, and function).
    

Detailed description: 
      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.
    

Intervention name(s): Probiotic; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Participants will consume 1 capsule containing 2 billion CFU of a Bacillus strain spore preparation once daily for 56 days; Participants will consume 1 capsule containing maltodextrin once daily for 56 days
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Bacillus; probiotic; bloating; microbiome; metagenomics; inestinal; permeability