Periodontopathogens Porphyromonas gingivalis and Fusobacterium nucleatum and Their Roles in the Progression of Respiratory Diseases

Abstract

The intricate interplay between oral microbiota and the human host extends beyond the confines of the oral cavity, profoundly impacting the general health status. Both periodontal diseases and respiratory diseases show high prevalence worldwide and have a marked influence on the quality of life for the patients. Accumulating studies are establishing a compelling association between periodontal diseases and respiratory diseases. Here, in this review, we specifically focus on the key periodontal pathogenic bacteria Porphyromonas gingivalis and Fusobacterium nucleatum and dissect their roles in the onset and course of respiratory diseases, mainly pneumonia, chronic obstructive pulmonary disease, lung cancer, and asthma. The mechanistic underpinnings and molecular processes on how P. gingivalis and F. nucleatum contribute to the progression of related respiratory diseases are further summarized and analyzed, including: induction of mucus hypersecretion and chronic airway inflammation; cytotoxic effects to disrupt the morphology and function of respiratory epithelial cells; synergistic pathogenic effects with respiratory pathogens like Streptococcus pneumoniae and Pseudomonas aeruginosa. By delving into the complex relationship to periodontal diseases and periodontopathogens, this review helps unearth novel insights into the etiopathogenesis of respiratory diseases and inspires the development of potential therapeutic avenues and preventive strategies.

Keywords: Fusobacterium nucleatum; Porphyromonas gingivalis; microbial interaction; oral microbiota; periodontal disease; respiratory disease; systemic disease.

Figure 1

Separate pathogenic effects of P. gingivalis and F. nucleatum. (A) Both P. gingivalis (P.g) and F. nucleatum (F.n) can promote the expression of MU5AC genes and proteins thereby causing increased mucus in the lungs. (B) F. nucleatum invades the lung and induces the production of IL-1β, IL-6, TNF-α, MMP-9, and MMP-12, leading to lung inflammation and degradation of the extracellular matrix and basement membrane of the airways and lungs. (C) P. gingivalis invades the lung and induces the production of IL-6, IL-8, TNF-α, MCP-1, and CRP, leading to lung inflammation. (D) Outer membrane vesicles (OMVs) secreted by P. gingivalis containing a variety of virulence factors, such as LPS, fimbriae, and C-terminal domain (CTD) proteins, on the one hand, cause changes in cell morphology and promote apoptosis. On the other hand, OMVs can disrupt the tight junctions between cells and destroy the respiratory barrier.

Figure 2

Synergistic pathogenic effects of P. gingivalis and F. nucleatum with respiratory pathogens. (A) P. gingivalis (P.g) induced the expression of platelet-activating factor receptor (PAFR), which promoted the invasion of respiratory epithelial cells by Streptococcus pneumoniae (S.p). Mixed infection with both bacteria significantly increased the levels of IL-1β, TNF-α, and IL-17 in the lungs, compared with S. pneumoniae infection alone. (B) P. gingivalis and P. aeruginosa (P.a) co-cultures can mutually invade respiratory epithelial cells, although P. gingivalis inhibited P. aeruginosa-induced apoptosis via the STAT3 signaling pathway during the early stage of co-infection. (C) F. nucleatum (F.n) and P. aeruginosa co-aggregate to form more complex biofilms and jointly invade respiratory epithelial cells. Co-infection of the two species effectively increased the levels of IL-1β, TNF-α, and IL-6 in the lungs.