Unveiling the complex extra‐oral colonization pathways and pathogenic mechanisms of Fusobacterium nucleatum, a heterogeneous oral pathogen

Abstract Fusobacterium nucleatum is a heterogeneous bacterium that includes four subspecies. It is not only an opportunistic pathogen of periodontitis but also can be frequently detected at the lesion sites of various systemic diseases. Extensive research has underscored the significant involvement...

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Main Authors: Zhiwei Guan, Houbao Qi, Qiang Feng
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:View
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Online Access:https://doi.org/10.1002/VIW.20240153
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author Zhiwei Guan
Houbao Qi
Qiang Feng
author_facet Zhiwei Guan
Houbao Qi
Qiang Feng
author_sort Zhiwei Guan
collection DOAJ
description Abstract Fusobacterium nucleatum is a heterogeneous bacterium that includes four subspecies. It is not only an opportunistic pathogen of periodontitis but also can be frequently detected at the lesion sites of various systemic diseases. Extensive research has underscored the significant involvement of F. nucleatum in the onset, progression, and therapeutic responses of numerous oral and systematic diseases. Given its convenient isolation from lesions, feasibility to cultivate in vitro, and diverse pathogenic pathways, F. nucleatum has emerged as a “model species” for elucidating the effects of oral pathogens on systemic human health. Here, we begin by introducing the taxonomic characteristics of F. nucleatum. Next, we explore F. nucleatum’s ability to adhere to and invade host cells, which serves as a critical prerequisite for its pathogenicity. Subsequently, we analyze the pathways through which F. nucleatum achieves ectopic colonization, revealing how it establishes infections in non‐oral sites such as the intestine and reproductive tract. Furthermore, we elaborate on F. nucleatum’s pathogenic mechanisms, particularly in cardiovascular diseases, adverse pregnancy outcomes, and cancer, focusing on how it modulates host immune responses through diverse virulence factors and signaling pathways. Finally, we summarize the advances in understanding the regulatory mechanisms underlying F. nucleatum’s pathogenesis. We aim to provide a theoretical foundation for developing clinical interventions targeting F. nucleatum and to offer insights and directions for future investigations into the pathogenesis of oral pathogens in systemic diseases.
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spelling doaj-art-6ddcd058af6443078a9104275e48fa712025-08-20T02:35:53ZengWileyView2688-39882688-268X2025-06-0163n/an/a10.1002/VIW.20240153Unveiling the complex extra‐oral colonization pathways and pathogenic mechanisms of Fusobacterium nucleatum, a heterogeneous oral pathogenZhiwei Guan0Houbao Qi1Qiang Feng2School of Life Science Qilu Normal University Jinan Shandong ChinaDepartment of Human Microbiome School and Hospital of Stomatology Cheeloo College of Medicine Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases Jinan ChinaDepartment of Human Microbiome School and Hospital of Stomatology Cheeloo College of Medicine Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases Jinan ChinaAbstract Fusobacterium nucleatum is a heterogeneous bacterium that includes four subspecies. It is not only an opportunistic pathogen of periodontitis but also can be frequently detected at the lesion sites of various systemic diseases. Extensive research has underscored the significant involvement of F. nucleatum in the onset, progression, and therapeutic responses of numerous oral and systematic diseases. Given its convenient isolation from lesions, feasibility to cultivate in vitro, and diverse pathogenic pathways, F. nucleatum has emerged as a “model species” for elucidating the effects of oral pathogens on systemic human health. Here, we begin by introducing the taxonomic characteristics of F. nucleatum. Next, we explore F. nucleatum’s ability to adhere to and invade host cells, which serves as a critical prerequisite for its pathogenicity. Subsequently, we analyze the pathways through which F. nucleatum achieves ectopic colonization, revealing how it establishes infections in non‐oral sites such as the intestine and reproductive tract. Furthermore, we elaborate on F. nucleatum’s pathogenic mechanisms, particularly in cardiovascular diseases, adverse pregnancy outcomes, and cancer, focusing on how it modulates host immune responses through diverse virulence factors and signaling pathways. Finally, we summarize the advances in understanding the regulatory mechanisms underlying F. nucleatum’s pathogenesis. We aim to provide a theoretical foundation for developing clinical interventions targeting F. nucleatum and to offer insights and directions for future investigations into the pathogenesis of oral pathogens in systemic diseases.https://doi.org/10.1002/VIW.20240153ectopic colonizationFusobacterium nucleatumoral pathogenpathogenic mechanismpro‐inflammatory effecttaxonomic characteristic
spellingShingle Zhiwei Guan
Houbao Qi
Qiang Feng
Unveiling the complex extra‐oral colonization pathways and pathogenic mechanisms of Fusobacterium nucleatum, a heterogeneous oral pathogen
View
ectopic colonization
Fusobacterium nucleatum
oral pathogen
pathogenic mechanism
pro‐inflammatory effect
taxonomic characteristic
title Unveiling the complex extra‐oral colonization pathways and pathogenic mechanisms of Fusobacterium nucleatum, a heterogeneous oral pathogen
title_full Unveiling the complex extra‐oral colonization pathways and pathogenic mechanisms of Fusobacterium nucleatum, a heterogeneous oral pathogen
title_fullStr Unveiling the complex extra‐oral colonization pathways and pathogenic mechanisms of Fusobacterium nucleatum, a heterogeneous oral pathogen
title_full_unstemmed Unveiling the complex extra‐oral colonization pathways and pathogenic mechanisms of Fusobacterium nucleatum, a heterogeneous oral pathogen
title_short Unveiling the complex extra‐oral colonization pathways and pathogenic mechanisms of Fusobacterium nucleatum, a heterogeneous oral pathogen
title_sort unveiling the complex extra oral colonization pathways and pathogenic mechanisms of fusobacterium nucleatum a heterogeneous oral pathogen
topic ectopic colonization
Fusobacterium nucleatum
oral pathogen
pathogenic mechanism
pro‐inflammatory effect
taxonomic characteristic
url https://doi.org/10.1002/VIW.20240153
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AT qiangfeng unveilingthecomplexextraoralcolonizationpathwaysandpathogenicmechanismsoffusobacteriumnucleatumaheterogeneousoralpathogen