Oral Pathobiont-Derived Outer Membrane Vesicles in the Oral-Gut Axis

Abstract

Oral pathobionts are essential in instigating local inflammation within the oral cavity and contribute to the pathogenesis of diseases in the gastrointestinal tract and other distant organs. Among the Gram-negative pathobionts, Porphyromonas gingivalis and Fusobacterium nucleatum emerge as critical drivers of periodontitis, exerting their influence not only locally but also as inducers of gut dysbiosis, intestinal disturbances, and systemic ailments. This dual impact is facilitated by their ectopic colonization of the intestinal mucosa and the subsequent mediation of distal systemic effects by releasing outer membrane vesicles (OMVs) into circulation. This review elucidates the principal components of oral pathobiont-derived OMVs implicated in disease pathogenesis within the oral-gut axis, detailing virulence factors that OMVs carry and their interactions with host epithelial and immune cells, both in vitro and in vivo. Additionally, we shed light on the less acknowledged interplay between oral pathobionts and the gut commensal Akkermansia muciniphila, which can directly impede oral pathobionts' growth and modulate bacterial gene expression. Notably, OMVs derived from A. muciniphila emerge as promoters of anti-inflammatory effects within the gastrointestinal and distant tissues. Consequently, we explore the potential of A. muciniphila-derived OMVs to interact with oral pathobionts and prevent disease in the oral-gut axis.

Keywords: OMVs; dysbiosis; inflammation; innate immunity; oral–gut axis; pathobionts; systemic disease; virulence factors.

Figure 1

Inflammation and gut dysbiosis induced by oral pathobionts. Outer membrane vesicles (OMVs) of Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) transport various virulence factors from the oral cavity to the gut and other distal organs via blood circulation. Subsequently, Pg and Fn could induce inflammation and gut dysbiosis through their OMVs. Created with BioRender (https://www.biorender.com/, accessed on 1 June 2024).

Figure 2

Proposed model for Akkermansia muciniphila-mediated regulation of oral pathobiont-induced disease at the oral–gut axis. Akkermansia muciniphila (Am) and its OMVs are suggested to exert protective effects, mitigating periodontitis in experimental models and reducing the expression of virulence factors in Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn). In the gut, Am contributes to maintaining barrier integrity and promoting the expansion of beneficial commensal species, thereby reducing the severity of colitis in mice. Additionally, Am may potentiate the efficacy of cancer immunotherapy. Up and down arrows indicate an increase or decrease in each indicated parameter, respectively. Question marks (shown as “?”) indicate areas where evidence is still inconclusive or remains to be explored. Created with BioRender.