Efficacy of probiotic supplementation in preventing Clostridioides difficile infection: an umbrella review of systematic reviews and meta-analysis

Background Clostridioides difficile infection (CDI) is a significant healthcare-associated infection. Probiotics have been proposed as a preventive strategy. This umbrella review synthesizes evidence from meta-analyses on the efficacy of probiotics in preventing CDI. Methods A comprehensive systematic search was conducted in PubMed, Scopus, Web of Science, Embase, and the Cochrane Library up to December 2025. To manage overlap, a single primary systematic review was selected per outcome. The methodological quality of included reviews was assessed using AMSTAR-2, and the certainty of evidence was graded. Pooled effect sizes were calculated using a random-effects model. Results Sixteen systematic reviews and meta-analyses were included. The pooled relative risk (RR) from primary reviews indicated that probiotics significantly reduced CDI risk (RR = 0.37; 95% CI: 0.32 to 0.42; I 2 = 0%). Multi-strain probiotics and formulations containing Saccharomyces boulardii showed significant benefits. The quality of evidence ranged from moderate to low, and overlap among primary studies was minimal (Corrected Covered Area = 15%). Conclusion Probiotic supplementation is associated with a reduced risk of CDI. However, given the variable methodological quality of the underlying evidence, these findings should be interpreted with caution. Population-specific and strain-specific effects require further investigation.