Comparative effectiveness of probiotics, prebiotics, synbiotics, and postbiotics in preventing dental caries: a meta-analysis from an oral microbiota modulation perspective

Dental caries remains one of the most prevalent non-communicable diseases worldwide, imposing substantial health and economic burdens despite conventional preventive measures such as fluoride use and oral hygiene. Increasing recognition of caries as a dysbiosis-driven biofilm disease has prompted exploration of microbiota-modulating strategies, including probiotics, prebiotics, synbiotics, and postbiotics. This systematic review and meta-analysis aimed to compare the effectiveness of probiotics, prebiotics, synbiotics, and postbiotics in preventing dental caries and to assess associated microbiological and ecological outcomes. A comprehensive search of MEDLINE, Embase, Cochrane CENTRAL, Web of Science, Scopus, trial registries, and grey literature was performed from inception to 2024. Randomized controlled trials and controlled clinical trials assessing caries outcomes or validated intermediate endpoints were included. Data extraction and risk-of-bias assessments were conducted independently by two reviewers. Random-effects meta-analysis was applied to estimate pooled risk ratios (RRs) with subgroup analyses by age, strain, delivery format, and duration. Certainty of evidence was graded using GRADE methodology. Twenty-five studies met inclusion criteria; 18 randomized trials contributed to meta-analysis. Probiotics demonstrated the strongest clinical signal. In pediatric populations (12 RCTs; n ≈ 2,300), probiotics significantly reduced new or progressive caries (RR = 0.80; 95% CI, 0.68–0.95). Adult probiotic trials (6 RCTs; n ≈ 1,100) showed no significant benefit (RR = 0.95; 95% CI, 0.80–1.12). Evidence for prebiotics (n = 3), synbiotics (n = 2), and postbiotics (n = 3) was sparse, heterogeneous, and largely limited to microbiological endpoints, including reductions in Streptococcus mutans and favorable plaque pH shifts. Reported adverse events were mild and infrequent. Probiotics, particularly Lactobacillus rhamnosus and L. reuteri delivered via lozenges or dairy products, show moderate-certainty evidence for modest caries prevention in children. Other microbiota-modulating approaches remain promising but under-investigated, constrained by small sample sizes, heterogeneous interventions, and lack of standardized outcomes. Probiotics represent a safe and acceptable adjunct to conventional preventive strategies in pediatric populations, though benefits are modest. Prebiotics, synbiotics, and postbiotics require further validation through large, long-term, strain-specific RCTs with standardized clinical endpoints and mechanistic analyses to clarify their role in caries prevention.