Spatial ecology of the <i>Capnocytophaga</i> genus in the human oral cavity

The human oral microbiome, a complex ecosystem of niche-specific communities influenced by local ecological factors, plays a critical role in health and disease. <i>Capnocytophaga</i> species are prevalent in the human mouth, often abundant in dental plaque and linked to both commensalism and pathogenicity, motivating a detailed study of their ecological and functional diversity. This study employs metapangenomics to reveal <i>Capnocytophaga</i> strain-level distributions and functional adaptations across distinct sites in the human oral cavity. Pangenomic, phylogenetic, and average nucleotide identity analyses enabled classification of unnamed genomes and identified 13 groups, of which 8 include validly named species, and the remainder are named using Human Microbial Taxon (HMT) designations in the Human Oral Microbiome Database (HOMD; https://www.homd.org/). Mapping metagenomic reads to the pangenome revealed a strong preference of most <i>Capnocytophaga</i> genomes for dental plaque (both supra- and subgingival), yet identified strain-level variants of <i>C. sputigena</i>, <i>C. gingivalis</i>, <i>C. granulosa</i>, and <i>C. leadbetteri</i> detected more often on the tongue. Among dental plaque-abundant taxa, functional analyses uncovered two clades: one with cbb3-type cytochrome oxidase that is tied to enhanced denitrification and could help the organism adapt to hypoxic zones, and another with bd-type ubiquinol oxidase, more suited to aerobic metabolism. Carbohydrate and amino acid metabolism pathways also differed between these clades. These findings identify metabolic adaptations that may underlie sub-specialization within the plaque habitat and highlight the strain-level diversity of <i>Capnocytophaga,</i> including low-prevalence strains that are preferentially detected in sites outside the primary plaque habitat of this taxon.<h4>Importance</h4>Understanding the ecological roles of <i>Capnocytophaga</i> in the oral microbiome is critical for deciphering its contributions to health and disease, including periodontal and systemic infections. This metapangenomics study reveals a pronounced specialization by <i>Capnocytophaga</i> to dental plaque (including supragingival, subgingival, and periodontal pockets) and identifies metabolic adaptations, such as distinct respiratory, carbohydrate, and amino acid pathways, that may drive niche-specific survival. These findings support the site-specialist hypothesis and enhance our understanding of oral microbial community structure, laying a foundation for future research into microbial interactions and targeted therapies for oral health.