BACKGROUND: Oral candidiasis is a common opportunistic fungal infection caused by the genus Candida that primarily affects immunocompromised individuals. However, the clinical application of antifungal agents still faces frequent side effects and antifungal resistance, highlighting the urgent need for alternative therapeutic options. This systematic review aimed to synthesize RCT evidence up to February 2025, comprehensively comparing clinical outcomes across various probiotic regimens, in order to assess the efficacy of probiotics for oral candidiasis. METHODS: A literature search was conducted to identify randomized clinical trials (RCTs) comparing probiotic regimens (multi-strain combinations or strain-specific interventions) with control groups. Thirteen RCTs were analyzed, using a classical frequentist meta-analysis model. Outcomes focused on the odds ratio (OR) of oral candidiasis (defined as CFU/mL > 10(3) or 10(4)) and heterogeneity across studies. The analysis integrated evidence up to February 2025 to comprehensively assess clinical outcomes. RESULTS: The meta-analytic OR was 0.38 (95% confidence interval (95%CI): 0.22, 0.68), indicating a beneficial effect of treatment; the I(2)index was 60.3%. Focusing on participants diagnosed with oral candidiasis or related diseases, the OR was 0.40 (95% CI, 0.23, 0.70), with an I(2)index of 18.2%. CONCLUSION: The treatment effect in the susceptible populations appeared to have lower heterogeneity and more stable outcomes, indicating that the application of probiotics is beneficial for oral candidiasis, and the effects vary according to the population characteristics and sample size. Owing to the small sample size and high-risk studies, the results should be interpreted with caution.
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