Efficacy and Safety of Streptococcus salivarius K12 for the Prevention of Upper Respiratory Tract Infections and Acute Otitis Media: A Systematic Review and Meta-Analysis

Purpose Streptococcus salivarius k12 (SsK12), is an oral probiotic with antimicrobial properties proposed for the prevention of upper respiratory tract infections (URTI) and acute otitis media (AOM). However, published studies remain heterogeneous and inconclusive regarding whether SsK12 is effective and safe as a preventive therapy. We conducted a systematic review and meta-analysis in order to reach a decisive conclusion on the topic at hand. Methods Our meta-analysis was conducted in accordance with PRISMA 2020 guidelines. Six databases were searched from inception to January 2026, for clinical trials evaluating SsK12 use in healthy or at-risk participants aged 1–80 years. Outcomes included the incidence of URTIs, including pharyngitis/tonsillitis, and AOM. Risk of bias was assessed using the RoB-2 and MINORS tools. Random-effects meta-analyses were performed, with subgrouping and sensitivity analyses conducted to explore heterogeneity if present. Results Sixteen studies were included in this systematic review, of which 12 studies were included in the meta-analysis. Across the included studies, SsK12 use was associated with a significant reduction in pharyngitis/tonsillitis, and non-specified URTI episodes, with a pooled IRR of 0.28 [95% CI 0.14; 0.58] and 0.24 [95% CI 0.10; 0.59]. Sensitivity analysis confirmed the significant findings and revealed a significant reduction in AOM episodes, with pooled IRR of 0.48 [95%CI 0.37; 0.61] for the pharyngitis/tonsillitis and 0.50 [95% CI 0.36; 0.69] for AOM. Moreover, subgroup analysis showed significant reductions in pediatric and adult populations. Colonization showed dynamic variations, while COVID-19 susceptibility exhibited a non-significant effect. Conclusion Evidence suggests potential benefits of SsK12; however, the significant heterogeneity and methodological differences preclude firm recommendations, highlighting the need for more clinical trials with unified methodologies.