Effect of Probiotics Duration, Delivery Vehicle, and Dose on caries-related variables: A Systematic Review and Meta-Analysis

Background: Probiotics have been proposed as a promising adjunctive strategy for caries prevention. However, uncertainty remains regarding the most effective protocol of administration. In this context, the aim of this review was to evaluate the effects of probiotic administration on caries-related variables, with particular attention to duration of use, delivery vehicle, daily dose, and strain characteristics where the available data allowed. Methods: PubMed and Scopus were searched for randomized controlled trials on probiotics in healthy subjects. Studies comparing probiotics with placebo, no treatment, or different probiotic regimens were included, focusing on outcomes related to mutans streptococci (MS), Lactobacillus spp. (LB), salivary buffer capacity, and plaque pH. Meta-analysis was conducted when at least three sufficiently comparable studies were available. Planned subgroup analyses or meta-regression by delivery vehicle, dose, strain category, and age group were considered but were not performed when subgroup sizes were too small or reporting was insufficient. Results: Forty-six studies met the inclusion criteria, and 13 were included in the meta-analysis. Probiotic administration was generally associated with reductions in MS counts, particularly when delivered through yogurt, milk, and lozenges. Meta-analysis demonstrated significant reductions at 7 days (effect size -0.56; 95%CI: -0.83 to -0.28), 14 days (-0.81), and 28 days (-0.92; 95%CI: -1.69 to -0.15), suggesting a time-dependent effect despite substantial heterogeneity. For LB counts, the pooled effect was not significant at 2 weeks (0.29; 95%CI: -0.33 to 0.91) but became significant at 1 month (0.43; 95%CI: 0.10 to 0.75). No significant effect was observed in salivary buffer capacity. Daily doses ranged from 106 to 1010 CFU, with no clear dose-response relationship. Conclusions: Probiotics may contribute to caries prevention mainly through reductions in MS counts, particularly after repeated administration. However, substantial heterogeneity in strains, doses, delivery vehicles, populations, and outcome measures prevents identification of a clearly superior vehicle, dose, or strain. Increases in Lactobacillus spp. counts should be interpreted cautiously, because lactobacilli may act as probiotic organisms in some contexts but are also associated with caries progression in acidic biofilm environments. Clinical significance: Probiotics may be a promising adjunct for caries prevention by reducing salivary mutans streptococci, especially after 2-4 weeks of use. However, no optimal strain, dose, or delivery vehicle can yet be recommended, and probiotics should complement, not replace, established preventive strategies.