The effect of probiotic supplementation on zonulin levels in healthy individuals – A systematic review and meta-analysis

Purpose Numerous studies have investigated the effects of widely used probiotics, which are regularly consumed by healthy individuals. However, a comprehensive summary of these effects is still lacking. One of the presumed benefits of probiotic consumption is supporting the intestinal barrier function by reducing permeability. Zonulin is a protein produced by intestinal and liver cells, and its elevated levels in the blood are associated with increased intestinal permeability. Materials/Methods We conducted a systematic search on 12 April 2024, in the MEDLINE, Embase, and Cochrane databases using a predefined search strategy registered in PROSPERO (CRD42022286137). A total of 9,217 articles were screened by two independent researchers. Data from 307 subjects across five studies were included in the meta-analysis of changes in blood zonulin concentration. Due to differences in measurement techniques, the standardized mean difference (SMD) was chosen as the effect measure. A random-effects model was applied using the inverse variance method to estimate SMD with confidence intervals (CI), considering the expected heterogeneity. Results The quantitative synthesis of the data indicated no significant difference in blood zonulin levels between the probiotic and control groups (SMD = (−)0.01; 95% CI: [−0.39; 0.37], P = 0.95). Conclusions Our findings do not support the hypothesis that probiotic supplementation affects blood zonulin levels, and thus, the impact on intestinal barrier integrity was not confirmed in healthy individuals.