Journal of oral microbiology · 2026
The role of Fusobacterium nucleatum outer membrane vesicles in disease and related mechanisms: a scoping review of pathogenesis and potential therapeutic applications.
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Luo Chunfeng, Li Zhiwen, Yi Fengyang, Wen Ping, Zou Ting, Jiang Shan, Jin Zuolin
Аннотация
OBJECTIVE: Fusobacterium nucleatum (F. nucleatum) has been implicated in the exacerbation of cancer development and metastasis. Outer membrane vesicles (OMVs) derived from Gram-negative bacteria have gained considerable attention as a message bridge between bacteria and host cells. This review aims to comprehensively explore the role of F. nucleatum OMVs in the pathogenesis of diseases, their interaction with host cells, and their potential as novel therapeutic targets or vector tools.
DESIGN: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science for studies published up to March 2026. Subsequently, the review was performed in accordance with the PRISMA-ScR guidelines.
RESULTS: Twenty-one studies were finally included in accordance with the predefined inclusion criteria. These studies suggest that OMVs derived from F. nucleatum contain multiple virulence factor proteins, including FadA, Fap2, and FomA, and are associated with inflammatory bowel disease, colorectal cancer, oral squamous cell carcinomas, and rheumatoid arthritis. F. nucleatum OMVs can be internalized by intestinal epithelial cells, leading to the downregulation of tight junction proteins. These vesicles also induce the release of proinflammatory cytokines through the activation of autophagy, the NF-кB signaling pathway, or the AIM2 inflammasome. Additionally, they promote macrophage polarization towards a proinflammatory phenotype, ultimately triggering a cascade of inflammatory responses. Furthermore, F. nucleatum OMVs enhance bacterial adhesion and autoaggregation, facilitate immune suppression, and promote tumor growth and metastasis. Notably, F. nucleatum OMVs also possess potential as engineered drug delivery vehicles for cancer immunotherapy.
CONCLUSION: This review summarizes the current evidence regarding the molecular mechanisms through which F. nucleatum OMVs interact with both immune and non-immune cells, as well as the identification and composition of these OMVs, providing insights into their potential for preventive and therapeutic applications.
DESIGN: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science for studies published up to March 2026. Subsequently, the review was performed in accordance with the PRISMA-ScR guidelines.
RESULTS: Twenty-one studies were finally included in accordance with the predefined inclusion criteria. These studies suggest that OMVs derived from F. nucleatum contain multiple virulence factor proteins, including FadA, Fap2, and FomA, and are associated with inflammatory bowel disease, colorectal cancer, oral squamous cell carcinomas, and rheumatoid arthritis. F. nucleatum OMVs can be internalized by intestinal epithelial cells, leading to the downregulation of tight junction proteins. These vesicles also induce the release of proinflammatory cytokines through the activation of autophagy, the NF-кB signaling pathway, or the AIM2 inflammasome. Additionally, they promote macrophage polarization towards a proinflammatory phenotype, ultimately triggering a cascade of inflammatory responses. Furthermore, F. nucleatum OMVs enhance bacterial adhesion and autoaggregation, facilitate immune suppression, and promote tumor growth and metastasis. Notably, F. nucleatum OMVs also possess potential as engineered drug delivery vehicles for cancer immunotherapy.
CONCLUSION: This review summarizes the current evidence regarding the molecular mechanisms through which F. nucleatum OMVs interact with both immune and non-immune cells, as well as the identification and composition of these OMVs, providing insights into their potential for preventive and therapeutic applications.