The Role of Oral Pathobionts' Outer Membrane Vesicles in Cancer Pathology and Therapeutic Development

Sep 22, 2026

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Cancer remains a leading cause of mortality worldwide, increasingly viewed through the lens of a modifiable host microbiome. Outer membrane vesicles (OMVs) from Gram-negative oral pathobionts act as nanoscale delivery systems carrying virulence factors, lipopolysaccharides, proteins, and nucleic acids. Evidence links OMVs from Porphyromonas gingivalis and Fusobacterium nucleatum to tumour-promoting inflammation, immune dysregulation, epithelial transformation, and metastatic progression. Mechanistically, OMVs activate signalling, disrupt mitochondria, induce oxidative stress, reprogram the tumour microenvironment, and may contribute to resistance to anticancer therapies. This review synthesizes roles in initiation, progression, and metastasis, discusses clinical associations, diagnostic biomarker potential, engineered OMVs for therapy, and key translational challenges.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages49

Reading Time2 h 3 min

AccessFree to download

Highlights

What are the main findings?

What are the implications of the main findings?

Abstract

Keywords

1. Introduction

Review The Role of Oral Pathobionts’ Outer Membrane Vesicles in Cancer Pathology and Therapeutic Development Sara Hadjigol *, Bansari A. Shah , Negar Yazdani and Neil M. O’Brien-Simpson * ACTV Research Group, Division of Basic and Clinical Oral Sciences, Centre for Oral Health Research, Melbourne Dental School, Royal Dental Hospital, The University of Melbourne, Carlton, Victoria 3010, Australia; [benny.shah@unimelb.edu.au](benny.shah@unimelb.edu.au) (B.A.S.); [negar.yazdani@student.unimelb.edu.au](negar.yazdani@student.unimelb.edu.au) (N.Y.) * Correspondence: [sara.hadjigol@unimelb.edu.au](sara.hadjigol@unimelb.edu.au) (S.H.); [neil.obs@unimelb.edu.au](neil.obs@unimelb.edu.au) (N.M.O.-S.) Highlights This review highlights that outer membrane vesicles from oral bacteria disrupt mitochondrial function, promoting inflammation, metabolic reprogramming, and tumour progression. What are the main findings? • Oral bacterial OMVs contribute to cancer initiation, progression, and metastasis. • OMVs from P. gingivalis and F. nucleatum promote chronic inflammation and immune evasion. • OMVs disrupt mitochondrial dynamics, inducing ROS production and metabolic reprogramming. • OMV-mediated signalling enhances tumour cell survival, invasion, and metastatic potential. • Engineered OMVs show promise as platforms for cancer immunotherapy and drug delivery. What are the implications of the main findings? • Oral health is directly linked to cancer risk, poor oral hygiene and periodontal disease may actively fuel tumour initiation and progression, making dental care a potential cancer prevention strategy. • A new mechanistic pathway to cancer has been identified, OMV-driven mitochondrial disruption and metabolic reprogramming represent a previously underappreciated route through which bacteria contribute to oncogenesis. • Tumour metastasis may be partially bacterially driven, the ability of OMVs to enhance invasion and metastatic signalling implicates oral dysbiosis as a systemic, not just local, threat. • Engineered OMVs open a new frontier in cancer therapy, their natural targeting and cargo-delivery properties make them compelling vehicles for immunotherapy and precision drug delivery, potentially with fewer side effects than synthetic nanoparticles. Academic Editor: Susmita Sil Received: 9 March 2026 Revised: 25 April 2026 Accepted: 30 April 2026 Published: 8 May 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. Abstract Cancer remains one of the leading causes of mortality worldwide, with increasing recognition of the host microbiome as a modifiable contributor to tumour initiation and progression. Among microbial mediators, outer membrane vesicles (OMVs) derived from Gram-negative oral pathobionts have emerged as critical effectors of host–microbe interactions. These nanoscale vesicles function as delivery systems for a diverse range of bioactive cargo, including virulence factors, lipopolysaccharides, proteins, and nucleic acids, enabling both local and systemic modulation of host cellular processes. Emerging evidence suggests that OMVs produced by oral pathobionts, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, are associated with tumour-promoting inflammation, immune dysregulation, epithelial transformation, and metastatic progression. Mechanistically, OMVs have been shown to activate key signalling pathways, disrupt mitochondrial function, induce oxidative stress, and reprogram the tumour microenvironment in ways that favour cancer cell survival and immune evasion. In addition, OMV-mediated modulation of host responses has been linked to resistance to anticancer therapies. In this review, we synthesize current evidence on the role of oral pathobionts’OMVs in cancer biology, with a focus on their contributi

FAQs

How do oral pathobionts’ outer membrane vesicles (OMVs) influence cancer development?

OMVs contribute to tumour initiation, progression, and metastasis by promoting tumour-associated inflammation, immune dysregulation, epithelial transformation, and signalling that enhances survival and invasion.

Which oral bacteria and mechanisms are highlighted in the review?

Porphyromonas gingivalis and Fusobacterium nucleatum OMVs are emphasized. Mechanisms include disruption of mitochondrial function and dynamics, induction of oxidative stress, activation of key signalling pathways, and reprogramming of the tumour microenvironment.

What therapeutic and diagnostic directions are discussed for OMVs?

Engineered OMVs are discussed as platforms for cancer immunotherapy and drug delivery, leveraging natural targeting and cargo delivery. The review also points to OMV-derived components as potential diagnostic biomarkers and emphasizes remaining translational challenges.

Sep 22, 2026

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