Fusobacterium nucleatum: a keystone bridging pathogen in polymicrobial biofilms and host immune dysregulation

Abstract

Oral infectious diseases such as periodontitis stem from disrupted homeostasis between host immunity and polymicrobial biofilm communities. Fusobacterium nucleatum, a ubiquitous oral commensal, is a key intermediate colonizer with well-documented interspecies coaggregation activity. It has been proposed as a bridging pathobiont that contributes to microbial dysbiosis and immune dysregulation at the host–microbe interface, though its in vivo structural bridging function remains debated. This mini-review synthesizes recent advances in understanding the dual functions of F. nucleatum in interspecies microbial interactions and host pathogenic crosstalk. We first delineate the molecular basis of its structural bridging role, focusing on surface adhesins FadA and Fap2 that mediate interspecies coaggregation, support colonization by late-periodontopathogens such as Porphyromonas gingivalis, and enable epithelial barrier invasion. We then dissect mechanisms by which F. nucleatum modulates innate and adaptive immune responses, propagating chronic inflammatory tissue damage while subverting host clearance pathways. Furthermore, we discuss synergistic pathogenicity with co-occurring pathogens and the systemic implications of disseminated F. nucleatum in extraoral disorders including colorectal cancer and adverse pregnancy outcomes. Finally, we highlight the translational promise of targeting F. nucleatum-mediated adhesion and immunomodulation as an ecological therapeutic strategy for oral infections and their systemic sequelae.