Fusobacterium nucleatum: a transboundary pathogen in host-microbiota networks

Fusobacterium nucleatum (Fn), a gram-negative anaerobic bacterium,, transitions from oral commensal to systemic pathogen in colorectal cancer (CRC), inflammatory bowel disease (IBD), arthritis, and preterm birth. This review synthesizes Fn's subspecies-specific pathogenic mechanisms. Its virulence factors enable immune evasion, inflammation modulation, and tumor progression. In the gastrointestinal tract, Fn disrupts intestinal barrier integrity through paracellular and apoptotic pathways, activates Th17/ T regulatory (Treg) immune balance alterations, and induces macrophage polarization. Moreover, Fn's role in tumorigenesis involves biofilm formation and metabolic regulation. Within microbial networks, Fn exhibits both synergistic and antagonistic interactions. It collaborates with pathogens like Clostridioides difficile and Pseudomonas aeruginosa to enhance infection, while being inhibited by probiotics such as Lactobacillus rhamnosus and Akkermansia muciniphila. Notably, microbial metabolites like butyrate and hydrogen sulfide display context-dependent roles-some may drive disease progression, while others may suppress it. This comprehensive review highlights Fn's pathogenicity and its complex interactions within microbial communities, offering novel interventions for microbiota-driven pathologies.