Saccharomyces Boulardii CNCM I-745 on Intestinal Barrier Function

This clinical trial, registered at ClinicalTrials.gov (NCT05538247) and conducted at the Mayo Clinic, is evaluating whether the probiotic yeast Saccharomyces boulardii CNCM I-745 can improve a 'leaky gut' — a condition where the lining of the intestine becomes less effective at controlling what passes from the gut into the rest of the body. Intestinal barrier dysfunction has been linked to a wide range of conditions including irritable bowel syndrome, inflammatory bowel disease, and systemic inflammatory disorders. Participants receive either the probiotic or a placebo, allowing researchers to isolate the effect of this specific yeast strain on permeability. S. boulardii CNCM I-745 is a well-characterized, non-colonizing yeast strain that has shown promise in prior smaller studies for stabilizing gut epithelial tight junctions and modulating local immune responses. The trial is completed as of May 2026, meaning results are anticipated soon. Because this is a randomized placebo-controlled design run at a major academic medical center, its findings will carry considerably more weight than preclinical or observational data. The key takeaway is that this study could provide high-quality human evidence for or against using this probiotic to treat measurable gut leakiness.

• Primary endpoint is a direct measure of intestinal permeability (specific assay not yet publicly reported, as results are pending); the study design positions this as a mechanistic, rather than symptom-based, outcome.
• The intervention arm uses the commercially available and well-characterized S. boulardii CNCM I-745 strain, enabling comparison with prior mechanistic data on tight-junction stabilization and anti-secretory protease secretion.
• As a completed but not yet published RCT at the Mayo Clinic, no efficacy or safety results are available in the public abstract; findings reported here reflect design intent and registered outcomes only (low confidence on outcome data).

This is a randomized, placebo-controlled clinical trial conducted at the Mayo Clinic, comparing S. boulardii CNCM I-745 supplementation against placebo in participants with impaired intestinal permeability. The primary outcome is a quantitative measure of intestinal barrier function, assessed through validated permeability testing (exact assay — e.g., lactulose/mannitol ratio or similar — not specified in the public registry record). Sample size, dosing regimen, and follow-up duration are not detailed in the available abstract; these details are best-effort inferences from the registry metadata (flag: low confidence on design specifics). The trial status is listed as completed with a primary completion date of May 11, 2026.

Because only the registry abstract is publicly available, no results, effect sizes, adverse event profiles, or population characteristics can be evaluated — all outcome-level statements carry low confidence. The study population, inclusion/exclusion criteria, and duration of supplementation are unknown from the current metadata, limiting generalizability assessment. It remains unclear whether the trial targets a specific disease context (e.g., IBS, post-infectious gut, or healthy volunteers with subclinical permeability elevation), which is critical for interpreting any permeability improvements in clinical context. The next logical experiment would be a dose-ranging or mechanism-focused follow-up pairing permeability outcomes with mucosal biopsy data (tight-junction protein expression, mucosal cytokine profiles) to explain HOW S. boulardii exerts its effects in humans.

This trial directly extends the mechanistic rationale described in [§144], which reviews molecular pathways by which probiotics support intestinal, neurologic, and cardiometabolic health, by providing a placebo-controlled human test of one specific probiotic mechanism — barrier permeability reduction. It parallels [§120], which investigates how Eubacterium rectale restores intestinal barrier integrity in gastrointestinal dysfunction, since both studies ask whether a single microorganism can meaningfully repair a leaky gut, albeit using different organisms and disease models. The study also parallels [§154], which examines FODMAP restriction mechanisms in functional gastrointestinal disorders, as both address measurable permeability changes through gut-targeted interventions in overlapping patient populations. More broadly, the trial sits in a growing corpus alongside [§153], which evaluates probiotic intervention on allergic disease development following early antibiotic exposure — a context where gut barrier disruption is also a putative mechanism — suggesting that S. boulardii's barrier-stabilizing effects, if confirmed here, could have implications well beyond GI disease alone.

• Eubacterium rectale Mitigates Inflammatory Bowel Disease via Modulation of Glutamine Metabolism Through the GLS2 and NF-κB Pathway
  Directly parallel question: both test whether a single microorganism (E. rectale vs. S. boulardii) can restore intestinal barrier integrity in GI dysfunction, making side-by-side mechanistic comparison highly informative.
• Molecular Pathways and Clinical Applications of Probiotics as Effective Supporters of Intestinal, Neurologic, and Cardiovascular Health: a Narrative Review
  Provides the mechanistic scaffolding — tight-junction modulation, immune signaling — that this RCT is designed to test clinically; reading together links molecular theory to human trial design.
• Mechanism of FODMAP Restriction on FGID Patients
  FODMAP restriction and probiotic supplementation are often co-investigated in functional GI disorders; comparing permeability outcomes across these two dietary/microbial approaches clarifies relative effect sizes.
• Probiotic Intervention on the Development of Allergic Diseases in Infants Exposed to Antibiotics Early in Life
  Both evaluate probiotics as a protective intervention in contexts of gut barrier compromise (antibiotic disruption vs. baseline permeability impairment), allowing comparison of strain-specific efficacy across different triggering conditions.
• Dietary Intervention with Brown Top Millet Starch Ameliorates Dyslipidaemia and Gut Leakiness in High Fat Diet Fed Models
  Examines dietary intervention on gut leakiness in a metabolic disease model, offering a non-probiotic comparator for the magnitude of permeability improvement achievable through gut-targeted interventions.