Polymicrobial synergy and dysbiosis in inflammatory disease

• Polymicrobial synergy and dysbiosis drive periodontitis in a susceptible host.
• Dysbiosis involves specialized accessory and keystone pathogens and pathobionts.
• Microbial immune subversion is central to the persistence of dysbiotic communities.
• The dysbiotic microbiota sustains itself by feasting on the ‘inflammatory spoils’.

Uncontrolled inflammation of the periodontal area may arise when complex microbial communities transition from a commensal to a pathogenic entity. Communication among constituent species leads to polymicrobial synergy between metabolically compatible organisms that acquire functional specialization within the developing community. Keystone pathogens, even at low abundance, elevate community virulence, and the resulting dysbiotic community targets specific aspects of host immunity to further disable immune surveillance while promoting an overall inflammatory response. Inflammophilic organisms benefit from proteinaceous substrates derived from inflammatory tissue breakdown. Inflammation and dysbiosis reinforce each other, and the escalating environmental changes further select for a pathobiotic community. We have synthesized the polymicrobial synergy and dysbiotic components of the process into a new model for inflammatory diseases.