Oral Biofilms from Symbiotic to Pathogenic Interactions and Associated Disease -Connection of Periodontitis and Rheumatic Arthritis by Peptidylarginine Deiminase

Abstract

A wide range of bacterial species are harbored in the oral cavity, with the resulting complex network of interactions between the microbiome and host contributing to physiological as well as pathological conditions at both local and systemic levels. Bacterial communities inhabit the oral cavity as primary niches in a symbiotic manner and form dental biofilm in a stepwise process. However, excessive formation of biofilm in combination with a corresponding deregulated immune response leads to intra-oral diseases, such as dental caries, gingivitis, and periodontitis. Moreover, oral commensal bacteria, which are classified as so-called "pathobionts" according to a now widely accepted terminology, were recently shown to be present in extra-oral lesions with distinct bacterial species found to be involved in the onset of various pathophysiological conditions, including cancer, atherosclerosis, chronic infective endocarditis, and rheumatoid arthritis. The present review focuses on oral pathobionts as commensal and healthy members of oral biofilms that can turn into initiators of disease. We will shed light on the processes involved in dental biofilm formation and also provide an overview of the interactions of P. gingivalis, as one of the most prominent oral pathobionts, with host cells, including epithelial cells, phagocytes, and dental stem cells present in dental tissues. Notably, a previously unknown interaction of P. gingivalis bacteria with human stem cells that has impact on human immune response is discussed. In addition to this very specific interaction, the present review summarizes current knowledge regarding the immunomodulatory effect of P. gingivalis and other oral pathobionts, members of the oral microbiome, that pave the way for systemic and chronic diseases, thereby showing a link between periodontitis and rheumatoid arthritis.

Keywords: P. gingivalis; oral biofilm; peptidylarginine deiminase; periodontitis; rheumatic arthritis.

FIGURE 1

Brief overview of current concepts regarding onset of periodontitis and rheumatic arthritis, and deduced causal relationships between both diseases. After establishing a subgingival biofilm, oral pathobionts, including Porphyromonas gingivalis, induce periodontitis as a chronic disease, which is attributable to host-pathobiont interactions and deleterious host immune responses in periodontal tissues. Dysregulated citrullination caused by the pathobiont Porphyromonas gingivalis has been suspected to be a causative factor for onset of rheumatic arthritis. Parts of this figure were taken from freely available web resources: https://www.chirurgie-portal.de/innere-medizin/rheuma.html; www.rcsb.org/pdb/ngl/ngl.do?pdbid=5AK7 (Rosenstein and Hildebrand, 2015; Montgomery et al., 2016).

FIGURE 2

Development of gingivitis and periodontitis. Following dental plaque accumulation, neutrophils dominate the host immune response, accompanied by progression of an early or stable gingivitis lesion, along with increased infiltration of macrophages and T cells. The gingivitis lesion develops into a periodontitis lesion, which is characterized by formation of a pathogenic periodontal pocket and destruction of periodontal tissues. Infiltrated lymphocytes are dominated by B and plasma cells.