Stratification of Fusobacterium nucleatum by local health status in the oral cavity defines its subspecies disease association

The ubiquitous inflammophilic oral pathobiont Fusobacterium nucleatum (Fn) is widely recognized for its strong association with inflammatory dysbiotic diseases and cancer. Fn is subdivided into four subspecies, which are historically considered functionally interchangeable in the oral cavity. To test this assumption, we analyzed patient-matched dental plaque and odontogenic abscess clinical specimens and examined whether an inflammatory environment selects for/against particular Fn subspecies. Dental plaque harbored a greater diversity of fusobacteria, with Fn. polymorphum dominating, whereas odontogenic abscesses were exceptionally biased for the largely uncharacterized organism Fn. animalis. Comparative genomic analyses revealed significant genotypic distinctions among Fn subspecies that correlate with their preferred ecological niches and support a taxonomic reassignment of each as a distinct Fusobacterium species. Despite originating as a low-abundance organism in dental plaque, Fn. animalis typically outcompetes other oral fusobacteria within the inflammatory abscess environment, which may explain its prevalence in other oral and extraoral diseases. [Display omitted] •Human dental plaque and oral abscesses harbor multiple types of oral fusobacteria•Fusobacterium nucleatum subspecies prevalence stratifies by ecological niches•F. nucleatum subsp. animalis predominates within the abscess environment•Comparative pangenomic analyses support taxonomic reclassification of F. nucleatum Kreiger et al. examine Fusobacterium nucleatum (Fn) subspecies prevalence in patient-matched clinical specimens of disease-free dental plaque vs. oral abscess. Fn. subsp. polymorphum is dominant within dental plaque, whereas the animalis subspecies dominates the abscess environment. Comparative pangenomic analyses of Fn reveal fundamental genotypic distinctions that support its taxonomic reclassification.