Abstract
BACKGROUND: Dental caries is a biofilm-dependent disease that continues to challenge conventional preventive strategies, such as fluoride application and mechanical plaque removal. Biofilm-targeted therapies (BTT), including probiotics, photodynamic therapy, enzymatic treatments, and natural compounds, represent promising alternatives to disrupt pathogenic biofilms effectively. However, the available evidence remains fragmented, with inconsistent methodologies and limited clinical data hindering comprehensive conclusions. METHODS: This systematic review and meta-analysis will synthesize evidence on the effectiveness of BTT in preventing and managing dental caries. A comprehensive search of PubMed (MEDLINE), Embase, and the Cochrane Library will identify randomized controlled trials (RCTs) and observational studies evaluating BTT interventions. To ensure methodological robustness, quantitative synthesis of intervention effectiveness will be restricted to RCTs, while observational studies will contribute to a structured narrative synthesis. Two independent reviewers will conduct study selection, data extraction, and risk of bias assessment using the RoB 2 tool for RCTs and ROBINS-I for observational studies. Where feasible, pairwise meta-analyses will be performed using random-effects models. If sufficient data are available, a network meta-analysis (NMA) will be considered. Subgroup and sensitivity analyses will explore the impact of age, caries risk level, and intervention type on treatment outcomes. DISCUSSION: This review anticipates providing evidence on the efficacy of BTT in reducing bacterial load, altering biofilm composition, and preventing caries progression. Variability in study design and outcome measures is expected, underscoring the need for standardized methodologies and more robust clinical trials. The findings aim to deliver evidence-based insights into the clinical applicability of BTT, addressing current knowledge gaps and guiding future research toward more effective caries prevention and management strategies. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42024615568.