Host-Microbe Mechanisms of Fusobacterium nucleatum in Colorectal Cancer.

Abstract

The oral-derived pathobiont Fusobacterium nucleatum has increasingly been implicated in colorectal cancer (CRC) progression through its ability to modulate inflammatory, immunological, and molecular pathways. F. nucleatum has emerged as a key oral-derived pathobiont frequently associated with tumor aggressiveness and alterations in the colorectal tumor microenvironment. This review critically examines recent mechanistic evidence from in vitro, in vivo, and advanced experimental models to elucidate how F. nucleatum interacts with host pathways involved in colorectal carcinogenesis. Available evidence indicates that this bacterium actively reshapes the tumor microenvironment through coordinated effects on immune signaling, epigenetic regulation, metabolic adaptation, and metastatic competence. Mechanistically, F. nucleatum promotes sustained inflammatory activation, macrophage polarization, epithelial-mesenchymal transition, endothelial remodeling, and resistance to regulated cell death pathways, while also influencing transcriptional and oncogenic programs associated with tumor progression. Emerging evidence further suggests that microbial effects may be modulated by tumor heterogeneity and long-term environmental exposures, reinforcing the complexity of host-microbiome interactions in CRC. Collectively, the findings support the concept that F. nucleatum functions as an active biological driver rather than a passive microbial bystander in CRC progression. These insights highlight the translational relevance of tumor-associated microbiota and support the need for approaches combining mechanistic, microbial, and clinical data to refine precision strategies at the tumor-microbiome interface.