Safety and efficacy of oral microbiome therapy for the treatment of recurrent Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials

Introduction This systematic review and meta-analysis aimed to assess the safety and efficacy of oral microbiome therapy (OMT) for the treatment of recurrent Clostridioides difficile infection (CDI).Methods A comprehensive search was performed in PubMed, Cochrane library, Scopus and Embase. All randomized controlled trials (RCTs) meeting predefined inclusion criteria were included. Statistical analysis was performed using R software.Results Three RCTs comprising 469 patients were analyzed, of whom 250 (53%) received OMT and 219 (47%) received placebo. OMT significantly reduced CDI recurrence at week 8 compared to placebo (risk ratio [RR] 0.57; 95% confidence interval [CI] 0.33–0.99; p = 0.04). In exploratory efficacy analyses, no significant differences in recurrence were observed between groups when stratified by prior fidaxomicin use (RR 0.36; 95% CI 0.03–4.01; p = 0.40) or vancomycin use (RR 0.68; 95% CI 0.30–1.55; p = 0.35). Similarly, Firmicutes engraftment at week 1 (mean difference [MD] 41.78; 95% CI −10.55 to 94.11; p = 0.12) and week 8 (MD 34.06; 95% CI −2.49 to 70.61; p = 0.07) did not show statistically significant between-group differences. Safety outcomes and adverse events were comparable between OMT and placebo.Conclusion OMT seems to reduce CDI recurrence at week 8 compared with placebo while demonstrating a comparable safety profile, supporting its role as an effective, well-tolerated therapy for recurrent CDI. New studies are necessary to confirm these findings.Registration The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251022230.