<i>Fusobacterium nucleatum</i> in cancer: from bystander to driver.

Abstract

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, <i>Fusobacterium nucleatum</i> (<i>Fn</i>), an oral commensal bacterium, has emerged as a significant oncobacterium implicated in tumour progression. The <i>Fn</i> 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 <i>Fn</i>'s function across different spatial locations and physiological states remains to be fully elucidated. This review details the genetic and phenotypic heterogeneity among <i>Fn</i> subspecies, which underlies their differential characteristics and niche adaptation. We further delineate key effectors of <i>Fn</i>, such as adhesins, metabolites and exoproteins, which collectively facilitate host cell invasion, immune evasion and chemoresistance induction. We explore the translational potential of <i>Fn</i>, underscoring its utility as a diagnostic biomarker and a promising target for novel therapeutic strategies.