Periodontitis: from microbial immune subversion to systemic inflammation

Abstract

Periodontitis is a dysbiotic oral disease that increases the patients' risk of developing systemic inflammatory disorders. The dysbiosis of the periodontal microbiota is characterized by an imbalance in the relative abundance or influence of microbial species with distinct roles that converge to shape a pathogenic microbial community. Within the community, periodontal bacteria use sophisticated strategies to evade immune-mediated killing while promoting a nutritionally favourable inflammatory response. The host response is initially subverted by keystone pathogens with the aid of accessory pathogens and is subsequently overactivated by the emerging pathobionts, which leads to destructive inflammation. Periodontal bacteria (including Porphyromonas gingivalis) have been detected in circulating leukocytes and in aortic tissues, where clinical and mechanistic animal-model studies indicate that they act as pro-atherogenic stimuli. P. gingivalis expresses a unique citrullinating enzyme that is involved in the generation of autoantibodies that contribute to the pathogenesis of rheumatoid arthritis. Bacteria that originate from the periodontal tissue (such as Fusobacterium nucleatum) have been detected in the placenta, where they can cause adverse pregnancy outcomes, as suggested by clinical and mechanistic evidence. The periodontal biofilm also acts as a reservoir for respiratory infections and for exacerbations of chronic obstructive pulmonary disease in synergy with local opportunistic pathogens. Understanding how oral pathogens subvert the host response at the molecular level will not only provide insights into the pathogenesis of periodontitis and associated systemic conditions, but could also reveal new therapeutic targets.