Metagenomic Insights Into the Subgingival Microbiome in Periodontal Health and Different Grades of Periodontitis

ABSTRACT Aim This cross‐sectional study compared the subgingival microbiome in periodontal health (PH) and periodontitis, focusing on distinguishing Stage III Grade B periodontitis (PD‐S3gB) and Stage III Grade C periodontitis (PD‐S3gC) as defined by the 2018 Classification of Periodontitis. Methods Subgingival samples from subjects with PH, PD‐S3gB, and PD‐S3gC were analyzed using metagenomic sequencing. Taxonomic and functional annotations were performed, followed by analyses of microbial diversity, differential abundance, interspecies networks, predictive modeling, and functional pathway enrichment. Results Significant differences in both alpha and beta diversity were observed between PH and periodontitis. Several periodontal pathogens were more abundant in disease states, with Capnocytophaga granulosa and Capnocytophaga sp. CM59 enriched in PD‐S3gC compared to PD‐S3gB. The PD‐S3gC group also exhibited a more complex microbial network with increased interspecies connectivity. An 11‐species diagnostic model effectively distinguished PH, PD‐S3gB, and PD‐S3gC. Furthermore, pathways related to motility, chemotaxis, and methane metabolism were significantly enriched in periodontitis. Conclusion Distinct structural and functional differences in the subgingival microbiome characterize periodontal health and periodontitis. Periodontitis with a rapid rate of progression is marked by specific pathogen overgrowth and enhanced microbial interactions, supporting the development of microbiome‐based diagnostics and personalized therapies. Trial Registration: Chinese Clinical Trial Registration: ChiCTR2000039426