Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology

Abstract

Recent advancements in the periodontal research field are consistent with a new model of pathogenesis according to which periodontitis is initiated by a synergistic and dysbiotic microbial community rather than by select 'periopathogens', such as the 'red complex'. In this polymicrobial synergy, different members or specific gene combinations within the community fulfill distinct roles that converge to shape and stabilize a disease-provoking microbiota. One of the core requirements for a potentially pathogenic community to arise involves the capacity of certain species, termed 'keystone pathogens', to modulate the host response in ways that impair immune surveillance and tip the balance from homeostasis to dysbiosis. Keystone pathogens also elevate the virulence of the entire microbial community through interactive communication with accessory pathogens. Other important core functions for pathogenicity require the expression of diverse molecules (e.g. appropriate adhesins, cognate receptors, proteolytic enzymes and proinflammatory surface structures/ligands), which in combination act as community virulence factors to nutritionally sustain a heterotypic, compatible and proinflammatory microbial community that elicits a non-resolving and tissue-destructive host response. On the basis of the fundamental concepts underlying this model of periodontal pathogenesis, that is, polymicrobial synergy and dysbiosis, we term it the PSD model.

Figure 1

The polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. The gingival crevice is colonized by a diverse microbiota, and compatible organisms assemble into heterotypic communities. These communities are in equilibrium with the host. Although they are proinflammatory and can produce toxic products such as proteases, overgrowth and overt pathogenicity are controlled by the host. The microbial constituents of the communities can vary over time, and from person to person and site to site. Colonization by keystone pathogens such as Porphyromonas gingivalis elevates the virulence of the entire community following interactive communication with accessory pathogens such as mitis group streptococci. Host immune surveillance is impaired and the dysbiotic community increases in number eventually disrupting tissue homeostasis and causing destruction of periodontal tissues.