Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host and cancer association

Abstract

The past decades of biomedical research have yielded massive evidence for the contribution of the microbiome in the development of a variety of chronic human diseases. There is emerging evidence that Porphyromonas gingivalis, a well-adapted opportunistic pathogen of the oral mucosa and prominent constituent of oral biofilms, best known for its involvement in periodontitis, may be an important mediator in the development of a number of multifactorial and seemingly unrelated chronic diseases, such as rheumatoid arthritis and orodigestive cancers. Orodigestive cancers represent a large proportion of the total malignancies worldwide, and include cancers of the oral cavity, gastrointestinal tract and pancreas. For prevention and/or enhanced prognosis of these diseases, a good understanding of the pathophysiological mechanisms and the interaction between P. gingivalis and host is much needed. With this review, we introduce the currently accumulated knowledge on P. gingivalis's plausible association with cancer as a risk modifier, and present the putative cancer-promoting cellular and molecular mechanisms that this organism may influence in the oral mucosa.

Keywords: Porphyromonas; cancer; cellular; molecular; oral microbiology.

Figure 1

Schematic representation of the complex interrelationships between different human genetic, behavioral and immunologic factors, as well as microbiome-related factors, that are proposed to take part in the multifactorial etiology of orodigestive cancers and other possibly associated chronic diseases. P. gingivalis is implicated to play a specific role in these multi-directional links. Dashed arrows represent plausible associations, based on currently available epidemiologic, clinical, histological, and experimental studies.

Figure 2

Postulated pro-cancer molecular circuitry of P. gingivalis and OECs interface that may affect the increased risk of orodigestive cancers and their poor prognosis. Over the period of its co-evolution with human oral mucosa, P. gingivalis has established multiple virulence factors such as distinctive fimbriae (FimA), cysteine proteases (gingipains), lipopolysaccharide (LPS), peptidyl-arginine deiminase (PAD), and nucleoside diphosphate kinase (NDK). These molecules, in concert with genetic predisposition, behavioral factors and possibly in synergy with other microbiome components, can elicit multiple pro-survival effects on the epithelial cells that may lead to predisposition for the cancerous transformation. Additionally, gingipains are suggested to play a role in the activation of MMPs, particularly MMP9, which are shown be associated in the metastatic dissemination of carcinoma cells.