We would also like to acknowledge the support of Dr J. Christopher Post, and appreciate the assistance of Ms Mary OToole in the preparation of this manuscript. “
“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 Epacadostat mouse 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 APO866 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. It is increasingly acknowledged that certain inflammatory diseases are associated with imbalances in the relative abundance or influence of microbial species within an ecosystem. This state is known as dysbiosis and leads to alterations in the host–microbe cross-talk that can potentially cause (or at least exacerbate) mucosal inflammatory disorders, such as inflammatory bowel disease, colo-rectal cancer, bacterial

vaginosis, and periodontitis [1, 2]. The host–microbe homeostasis that characterizes a healthy mucosal tissue could be potentially destabilized by host-related factors such as diet, antibiotics, and immune deficiencies. Moreover, perturbations to the host–microbe ecosystem could also be precipitated by increased expression of microbial virulence factors that PLEK2 subvert the host immune response [3-5]. As a potential disease trigger, dysbiosis stands in stark contrast to the traditional view of a classic infection caused by a single or several select pathogens. An exemplar of this changing paradigm is periodontitis, a prevalent chronic inflammatory condition that leads to the destruction of the tooth-supporting tissues (periodontium) and potentially to systemic complications [6, 7]. Recent advances in this field are consistent with a new model of periodontal pathogenesis, according to which periodontitis is initiated by a synergistic and dysbiotic microbial community rather than by select “periodontal pathogens” as traditionally thought [2, 8].