Fusobacterium nucleatum in cancer: from bystander to driver

The human microbiota comprises a diverse and extensive community of microorganisms that participate in intricate interactions with the host, several of which are increasingly acknowledged as key modulators of health and disease. Among these, Fusobacterium nucleatum (Fn), an oral commensal bacterium, has emerged as a significant oncobacterium implicated in tumour progression. The Fn genus comprises distinct subspecies, clades and strains, exhibiting marked phylogenetic and physiological heterogeneity. Consequently, pinpointing the true functional modulators within this complex community and elucidating their mechanisms in various physio-pathological states remains a critical yet challenging endeavour. Moreover, the complete mechanism underlying Fn's function across different spatial locations and physiological states remains to be fully elucidated. This review details the genetic and phenotypic heterogeneity among Fn subspecies, which underlies their differential characteristics and niche adaptation. We further delineate key effectors of Fn, such as adhesins, metabolites and exoproteins, which collectively facilitate host cell invasion, immune evasion and chemoresistance induction. We explore the translational potential of Fn, underscoring its utility as a diagnostic biomarker and a promising target for novel therapeutic strategies.