Antibiotic Resistance Genes in the Subgingival Microbiome in Periodontitis: A Scoping Review of Prevalence, Mobility, and Future Directions

The objective of the study is to evaluate the prevalence, diversity, and mobility of antibiotic-resistant species and resistance genes within the subgingival microbiome of patients with periodontitis. A systematic scoping review was conducted in accordance with PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Five electronic databases were searched for studies published between January 2020 and December 2025 that used molecular techniques (shotgun metagenomics, PCR/qPCR, 16S + PCR) to detect antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in the subgingival plaque of patients with clinically diagnosed periodontitis. Only peer-reviewed articles presenting original data were included; reviews, animal studies, and investigations lacking clear methodological details were excluded. Data extraction included study design, sample size, identified ARGs, associated MGEs, and clinical context. Nine eligible studies involving over 900 subgingival samples were identified. A core resistome was consistently identified across all cohorts, predominantly comprising tetracycline genes (tetM, tetQ, tet32) and macrolide-lincosamide determinants (ermB, ermF, msrD), as well as β-lactamase genes such as cfxA. Sites affected by periodontitis showed higher abundance of these ARGs than healthy controls. Mobile elements, especially Tn916-family conjugative transposons, were often associated with macrolide resistance genes, suggesting potential for horizontal transfer. Methodological differences prevented meta-analysis, and no study compared results based on the 2017 stage/grade classification of periodontitis. The subgingival resistome in periodontitis features a consistent set of tetracycline, macrolide, and β-lactam resistance genes that are increased in disease and frequently associated with mobile transposons. Currently, the evidence remains primarily descriptive; future research should include standardized antibiotic washout periods, longitudinal follow-up, stage/grade stratification, and integrated multi-omics approaches to evaluate functional activity and guide personalized antimicrobial therapies.