Table 1.

Milestones and hypotheses in the microbial etiology of periodontitis¹

Chronology	Etiology or key concepts	Remarks	References
Late 19th to early 20th century	Specific microorganisms (amebae, spirochetes, fusiforms or streptococci)	Based on apparent association with periodontal lesions; heavily biased by technique used (wet-mount microscopy, stained smear microscopy, and limited cultural methods)	Meyer (1917)
Mid-1920s to 1930s	Decline in the interest in bacteria as primary agents in the etiology of periodontitis	Disease primarily due to defects in the patient (e.g. trauma from occlusion); bacteria are simply secondary invaders or at best contributors to the disease process	Bruske (1928) and Belding & Belding (1933)
Late 1950s	‘Non-specific plaque hypothesis’ and its variant, ‘Mixed anaerobic infections’	Sufficient accumulation of any microorganisms at or below the gingival margin can cause destructive inflammation through the local production of ‘irritants’ Bacteriologically non-specific but biochemically specific mixed anaerobic infections are capable of producing destructive metabolites	Schultz-Haudt et al. (1954) and Macdonald et al. (1956)
Late 1970s to early 1980s	Microbial shift in periodontitis	Dramatic compositional changes to the microbiota in disease as compared with health	Slots (1977a,b), Socransky (1977), Tanner et al. (1979) and Moore et al. (1982, 1983)
	‘Specific plaque hypothesis’	Periodontitis results, at least in significant part, from the overgrowth of specific pathogenic species	Loesche (1979, 1992)
Late 1980s to 1990s	‘Red complex’	Periodontal microbial communities characterized on the basis of a color-coded system reflecting cluster analysis, community ordination, and associated disease severity. A group of ‘red complex’ bacteria (Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia) are strongly associated with each other and with diseased sites. Porphyromonas gingivalis causes periodontitis in nonhuman primates upon its oral implantation	Holt et al. (1988) and Socransky et al. (1998)
2003	‘Ecological catastrophe hypothesis’	Environmental factors drive the selection and enrichment of specific pathogenic bacteria	Marsh (2003)
2010	Disruption of periodontal tissue homeostasis	Periodontitis fundamentally represents disruption of tissue homeostasis; inflammation is critical but a secondary event. Red complex bacteria are key species for disease, although the polymicrobial nature of periodontitis is acknowledged; commensal bacteria probably induce a protective response	Darveau (2010)
2011	‘Keystone pathogen’ concept	Low-abundance keystone species can disrupt tissue homeostasis through quantitative and qualitative changes to the commensal microbiota (resulting, at least in great part, from host modulation by the keystone pathogen). Inflammatory bone loss is mediated by the altered microbiota	Hajishengallis et al. (2011)
2012	‘Polymicrobial synergy and dysbiosis’ (PSD)	Periodontitis is initiated by a synergistic and dysbiotic microbiota, within which different members, or specific gene combinations thereof, fulfill distinct roles that converge to shape and stabilize a disease- provoking microbiota. Combines the concepts of ‘disrupted homeostasis’ and ‘keystone pathogen’ but questions the primary importance of the red complex	This paper

¹For a detailed historic description of the various hypotheses, the reader is referred to Socransky & Haffajee (1994).