SYSTEMATIC REVIEW article
Front. Nutr.
Sec. Clinical Nutrition
Efficacy of Probiotic Supplementation in Preventing Clostridioides difficile Infection: An Umbrella Review of Systematic Reviews and Meta-analysis
Provisionally accepted
- Rehabilitation Medicine Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Wenzhou, China
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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; I² = 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%). Conclusions: 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.
Keywords: Clostridioides difficile infection, Meta-analysis, Probiotics, Systematic review, Umbrella
Received: 04 Sep 2025; Accepted: 05 Feb 2026.
Copyright: © 2026 Chen, Pan, Ji, Wu and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jing Ji
Xinxin Lin
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