Reinforcing gut integrity: A systematic review and meta-analysis of clinical trials assessing probiotics, synbiotics, and prebiotics on intestinal permeability markers.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized clinical trials.
PubMed 40378939 · doi:10.1016/j.phrs.2025.107780
What was done
A systematic review and meta-analysis searched Medline and Scopus from 1961 to January 2023 for clinical trials evaluating the impact of probiotics, synbiotics, or prebiotics on markers of intestinal permeability. The review identified 46 studies on probiotics and synbiotics and 22 studies on prebiotics. Standardized mean differences (SMD) with 95% confidence intervals (95% CI) were calculated using a random-effects model, and heterogeneity was assessed with Galbraith plots and Cochrane Chi-squared tests.
What was found
Pro- and synbiotic supplementation significantly decreased lipopolysaccharide (LPS) levels across 24 trials (28 effect sizes, n = 1,603; SMD = -0.54, 95% CI: -1.01 to -0.07; I² = 94.4%, very low certainty of evidence) and significantly lowered zonulin levels across 13 trials (15 effect sizes, n = 778; SMD = -0.49, 95% CI: -0.79 to -0.18; I² = 74.9%, moderate certainty of evidence). Prebiotic supplementation significantly reduced LPS levels across 16 RCTs (n = 792; SMD = -0.88, 95% CI: -1.28 to -0.47, p < 0.001; I² = 85.7%, high certainty of evidence).
Why it matters
This meta-analysis aggregates clinical trial evidence showing that targeted microbiome interventions, including prebiotics and probiotics, can moderately to strongly decrease indirect circulating biomarkers of gut barrier breakdown.
Limits
Statistical heterogeneity was substantial across all primary analyses (I² ranging from 74.9% to 94.4%). The certainty of evidence for LPS reduction by pro- and synbiotics was graded as very low. The abstract does not specify underlying participant clinical conditions, specific probiotic strains, prebiotic types, intervention durations, or direct functional measures of gut permeability (e.g., lactulose/mannitol excretion).
Cited by
- supports Probiotic and prebiotic supplementation supports a healthy gut microbiome.