Abstract
Recent metagenomic and mechanistic studies are consistent with a new model of periodontal pathogenesis. This model proposes that periodontal disease is initiated by a synergistic and dysbiotic microbial community rather than by a select few bacteria traditionally known as "periopathogens." Low-abundance bacteria with community-wide effects that are critical for the development of dysbiosis are now known as keystone pathogens, the best-documented example of which is Porphyromonas gingivalis. Here, we review established mechanisms by which P. gingivalis interferes with host immunity and enables the emergence of dysbiotic communities. We integrate the role of P. gingivalis with that of other bacteria acting upstream and downstream in pathogenesis. Accessory pathogens act upstream to facilitate P. gingivalis colonization and co-ordinate metabolic activities, whereas commensals-turned pathobionts act downstream and contribute to destructive inflammation. The recent concepts of keystone pathogens, along with polymicrobial synergy and dysbiosis, have profound implications for the development of therapeutic options for periodontal disease.