Reexamining the role of Fusobacterium nucleatum subspecies in clinical and experimental studies

The Gram-negative anaerobic species Fusobacterium nucleatum was originally described as a commensal organism from the human oral microbiome. However, it is now widely recognized as a key inflammophilic pathobiont associated with a wide variety of oral and extraoral diseases. Historically, F. nucleatum has been classified into four subspecies that have been generally considered as functionally interchangeable in their pathogenic potential. Recent studies have challenged this notion, as clinical data reveal a highly biased distribution of F. nucleatum subspecies within disease sites of both inflammatory oral diseases and various malignancies. This review details the historical basis for the F. nucleatum subspecies designations and summarizes our current understanding of the similarities and distinctions between these organisms to provide important context for future clinical and laboratory studies of F. nucleatum.