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Year : 2017  |  Volume : 8  |  Issue : 3  |  Page : 121-125

Periodontal disease – Historical and contemporary hypothesis: A review

1 Department of Periodontology and Oral Implantology, JSS Dental College and Hospital, JSS University, Mysuru, Karnataka, India
2 Department of Public Health Dentistry, JSS Dental College and Hospital, JSS University, Mysuru, Karnataka, India
3 Department of Periodontology, JSS Dental College and Hospital, Mysuru, Karnataka, India

Date of Web Publication18-Sep-2017

Correspondence Address:
Swet Nisha
Department of Periodontology, JSS Dental College and Hospital, Room No. 9, SS Nagar, Bannimantap, Mysuru - 570 015, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/srmjrds.srmjrds_15_17

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Dental plaque is a biofilm which is the prime etiological factor in the causation of oral diseases such as dental caries and periodontal disease. The various hypothesis has been developed explaining the pathogenesis of periodontal disease. Although a classical model to support this polymicrobial disease is yet to be proposed, all the stated hypothesis gives us a better idea in understanding the pathophysiology of the periodontal disease process.

Keywords: Dental plaque, dysbiosis, ecological plaque hypothesis, keystone pathogen hypothesis, nonspecific plaque hypothesis, specific plaque hypothesis

How to cite this article:
Nisha S, Samyuktha GS, Shashikumar P, Chandra S. Periodontal disease – Historical and contemporary hypothesis: A review. SRM J Res Dent Sci 2017;8:121-5

How to cite this URL:
Nisha S, Samyuktha GS, Shashikumar P, Chandra S. Periodontal disease – Historical and contemporary hypothesis: A review. SRM J Res Dent Sci [serial online] 2017 [cited 2022 May 24];8:121-5. Available from:

  Introduction Top

Dental plaque is a microbial biofilm generally considered to be an etiologic factor for the periodontal diseases. Loe et al. demonstrated the direct etiologic correlation between microbial biofilm and occurrence of gingivitis.[1] In retrospective, the theories that were initially utilized to discuss the association of biofilm with the disease were looking into either the biofilm's quality (specific plaque hypothesis) or quantity (nonspecific plaque hypothesis).

Such a profound correlation has not been causatively proven to exist between periodontitis and microbial biofilm. The host susceptibility and environmental factors also come into play and modify the action of biofilm and give us an idea about individual treatment strategies to combat the disease.

Dental plaque changes are related to health and disease, and this review aims at a discussion of main hypothesis of oral disease development and their implications.

The ideas about oral disease development have evolved overtime. In the nineteenth century, scientists could not identify bacteria related to disease due to the lack of technology. This led to the “Nonspecific Plaque Hypothesis” which states that the indigenous oral bacterial in the absence of oral hygiene colonize the gingival crevice to form plaque. Inflammation becomes when host resistance is lowered, and elimination of plaque leads to a healthy state. The theory illustrated that the quantity of plaque that determined the pathogenicity without discriminating between the levels of virulence of bacteria. Hence, the emphasis on plaque control agents to reduce the inflammation and periodontal status was given by this theory.[2],[3]

This theory focused on plaque mass, i.e. quantity and not on particular species which can play major role in etiopathogenesis and removal of only such species can reduce the whole microbial load and shift to the synergistic environment. Due to the lack of identification of individual species contribution in periodontal disease pathogenesis, this hypothesis nonspecifically targeted the disease.

Specific plaque hypothesis targets specific pathogen like red complex in the etiology of periodontal disease and targets on the elimination of these agents for periodontal health. This theory states that specific plaque is responsible for alteration in the microbiota of periodontal pocket which leads to periodontal disease.[4] The treatment aims are the removal of the specific pathogen through nonsurgical periodontal therapy, chemical plaque control agent. The specificity of plaque is difficult to determine, and many microorganisms which act as pathoboint, commensals, and many species remain to cultivate.[5] This hypothesis proposed that use of antibiotics against specific bacterial species could cure and prevent caries. Long term use of antibiotic caused antibiotic resistance and cessation of treatment lead to a reversal of climax community, new climax community more resistance to the antibiotic action.[6]

These suggested “specific-pathogens” are part of the indigenous microflora and unlike foreign pathogens cannot be eliminated from the oral cavity.

Bacterial culturing enlightened the role of specific bacteria in periodontal disease pathogenesis and its eradication through, chemical, physical means was suggested as treatment planning, but complete removal of microbial flora was difficult to achieve and commensals bacterial community were removed in lieu of antibiotic administration.

  Updated Nonspecific Plaque Hypothesis Top

Else Theilade noticed that in the absence of toothbrushing the gingival crevice is colonized by the complex indigenous microflora causing gingivitis, a nonspecific inflammation. Subgingival plaque may develop by downgrowth into the inflamed pocket of those microorganisms form supragingival plaque.[3]

Ecological changes favor subgingival colonization which results in destructive periodontitis. These changes increase the number of microorganisms and alter their proportions. The subgingival microorganisms have several virulence factors which promote colonization of the pockets, destroys host defence mechanism, and provoke inflammation.

It appears that different indigenous bacteria rather than just single species can produce the pathogenic potential necessary to cause progression from gingivitis to periodontitis. The “specific-pathogens” from the SPH were indigenous bacteria and sometimes common bacteria in health, which led to an updated NSPH in 1986 focusing on the periodontal disease.[3] The updated NSPH could explain this by taking into account that differences in the plaque microbial composition could lead to differences in pathogenic potential.

  Ecological Plaque Hypothesis Top

In 1994, Philip D. Marsh proposed a hypothesis that combined key concepts of the earlier hypotheses. In his “Ecological Plaque Hypothesis,” disease is the result of an imbalance in the total microflora due to ecological stress, resulting in an enrichment of some “oral pathogens” or disease-related micro-organisms.[7]

Marsh expanded this theory and related the changes in microbial composition to changes in ecological factors such as the presence of nutrients and essential cofactors, pH, and redox potential.[8] This lowers the redox potential giving strict anaerobes a chance to settle and multiply in the biofilm. Bacterial growth is dictated by the environment, Bacterial growth is dictated by the environment, which in turn is influenced by bacterial metabolism, a chain of events leads to disease and mutual dependencies between host and bacteria plays a major role in disease causation.[9] Disease could be prevented not only by inhibiting the periodontopathogens directly but also by interfering with the factors driving the transition, i.e., (i) reduction in Ph challenge – antimicrobial agents, (ii) altering the subgingival environment-anti-inflammatory agents, redox agents (iii) replacement therapy-preemptive colonization, competitive displacement were the treatment strategies to prevent periodontal disease.

This hypothesis gave emphasis on the role of environment on periodontal disease, oxidant balance plays a role, and microbial colonies in favorable environment acts synergistically to cause disease.

  Keystone Pathogen Hypothesis Top

Ecological literature characterizes keystone species as that have disproportionately large effects on their communities, given their abundance, and that are thought to form the “keystone” of the community's structure. In architecture, the keystone is the central supporting stone at the apex of an arch.[10]

A keystone microorganism that supports and stabilizes the dysbiotic microbiota associated with a disease state is referred to here as a keystone pathogen. Identification of such species can give us an insight into the structure of microbial communities and the interplay with their hosts or environment.

Hajishengallis applied this concept to oral microbiology by proposing “The Keystone-Pathogen Hypothesis” (KPH).[11] The KPH indicates that certain low-abundance microbial pathogens can cause inflammatory disease by increasing the quantity of the normal microbiota and by changing its composition.[12],[13] This concept was developed by observing the properties of the “red complex” bacterium Porphyromonas gingivalis.

Keystone pathogens can trigger inflammation when they are present in low numbers, and as the disease develops and advanced stages are reached, the keystone pathogen is detected in higher numbers.[13] The role of the host-immune system is critical in the KPH. At health, periodontal tissue contains a wall of neutrophils, between the plaque and the epithelial surface, residing just outside the epithelial cells. Expression of mediators such as interleukin 8 (IL-8), intercellular adhesion molecule, and E-selectin is required to form this neutrophil wall.[14]

Three major mechanism by which P. gingivalis act are (1) toll-like receptor (TLR) response manipulation, (2) IL-8 subversion, and (3) the corruption of the complement system.[15],[16]

During inflammatory process, gingival crevicular fluid increases indicating that P. gingivalis Type II LPS expression increases which reduce the TLR4 response. It was proposed that this could facilitate survival and multiplication of the entire microbial community.[17]

P. gingivalis can block production of IL-8 in vitro, by secreting serine phosphatase that inhibits the synthesis of IL-8, process is called “local chemokine paralysis” and delays the recruitment of neutrophils preventing proper neutrophil wall formation, of which was proposed that it could facilitate initial microbial colonization of the periodontium.[18]

The complement system is a major component of the innate immune response involved in recognizing and destroying microorganisms. P. gingivalis has cysteine protienases called gingipains that cleaves complement factors C3 and C5 into active fragments C5a and C3b. C5aR is involved in crosstalk with TLR2, which is activated in parallel by P. gingivalis. This accelerates alveolar bone loss and credited mainly due to the complement subversion.[19]

Thus, a keystone pathogen is an agent that remodels the commensal microbiota into a dysbiotic state by causing disruption of host homeostasis. A keystone pathogen does not rely on already disrupted host homeostasis to cause disease, as proposed for “pathobionts” which are not necessarily low-abundance species and promote chronic inflammatory pathology only in hosts with specific genetic or environmental alterations.[20]

Strategies targeting the keystone pathogen can change the dysbiotic flora to normal commensals and identify such pathogens is the future challenge in combating the periodontal disease.

  The Polymicrobial Synergy and Dysbiosis Model of Periodontal Disease Etiology Top

This hypothesis is broadly based on dysbiotic, synergistic, microbiota, as opposed to the traditional view of a conventional infectious disease caused by a single or even several select periopathogens, such as the “red complex.” It highlights the importance of other bacteria in keystone pathogenesis and the thought that other than the classical “red complex” species could have similar key-stone roles in periodontitis.[21] It states that in periodontitis polymicrobial synergy can lead to dysbiosis.

The core requirements for a potentially pathogenic community to arise are:[21]

  • Bacterial constituents will express the relevant adhesins and receptors to allow assembly of a heterotypic community
  • Individual members of the community will be physiologically compatible or at least nonantagonistic
  • The combined activities of the community will resist the host innate and acquired immune responses and contribute to tissue inflammation.

These organisms engage in two-way communication with the community inhabitants, in particular, the accessory pathogens, to both disrupt host immune surveillance and elevate the pathogenicity of the entire group.

The capacity of P. gingivalis to exert a community-wide impact that tipped the balance toward dysbiosis while being a quantitatively minor constituent of this microbial community, has prompted its characterization as a keystone pathogen, in analogy to the crucial role of a single keystone in an arch.[22]

Specifically, P. gingivalis, at low colonization levels (<0.01%) of the total microbiota), remodeled a symbiotic community into a dysbiotic state that triggered an inflammatory bone loss.[23] Polymicrobial synergy among periodontal pathogens, therefore, extends beyond growth rate effects and involves interspecies signaling and response interactions.

  Periodontal Diseases and the Fusion of Nonspecific, Ecological and Keystone Pathogen Hypotheses Top

Periodontal diseases”gingivitis and periodontitis do not fit to a single hypothesis. The intimate interaction of bacteria with the host leading to inflammatory reaction adds to the complexity of these diseases [Table 1].
Table 1: Summary of different hypothesis

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Periodontitis results from complex interactions of microorganisms and the immune system. Due to increased plaque amount and increased abundance of more virulent and keystone pathogen bacteria, the concentration of inflammatory mediators increases. An increase in the concentration of pro-inflammatory cytokines in periodontal tissue can directly affect bone loss.

The diverse microbiome has commensals and mutualism with the host and is maintained by bacterial homeostasis – a balance of intermicrobial and host microbial interactions.[7]

With the KPH, the periodontal diseases, especially periodontitis, heavily depend on a single periodontal bacterium — P. gingivalis. This is probably due to the relative ease of cultivation and genetic modification compared to the other species.[16] Other species might be equally or even more active in the process that leads from periodontal health to disease and should be investigated.

Role of the virus as an etiologic agent in periodontitis has been identified, its re-activation theory suggests the burst activity of periodontitis.[24]

Any hypothesis is broadly based on the etiologic agent focused in a particular era, and treatment planning is targeted towards removal of etiogenic agent. The futuristic application should be based on application of hypothesis to prevent the disease process, especially aggressive, refractory cases.

Evidence-based approach will help us to choose correct treatment planning and patient satisfaction. Knowledge of pathogenesis will guide the practitioner in correct diagnosis and prognosis of the disease. Genetic-based hypothesis can solve many systemic associated periodontal manifestation and progressive forms of the disease.

  Conclusion Top

All presently available hypotheses fall short of combining actual microbial and host behavior that lead to maintenance of health or the shift to disease. Although they give us an idea about periodontal disease pathogenesis, a holistic approach is required. The various hypotheses help in better understanding of the pathogenesis and disease progression. Although each having its limitations, a comprehensive review of past hypothesis will help in finding the lacunae and understanding the disease process.

Use of advanced microbial aids – metagenome, transcriptome can help us provide more information on oral ecology, identify uncultivable the oral species. Future research can unravel the mechanism of periodontal disease and help in management and its prevention.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Loe H, Theilade E, Jensen SB. Experimental gingivitis in man. J Periodontol 1965;36:177-87.  Back to cited text no. 1
Miller WD. The Micro-Organisms of the Human Mouth. Philadelphia, PA: The S.S. White Dental MFG. Company; 1890.  Back to cited text no. 2
Theilade E. The non-specific theory in microbial etiology of inflammatory periodontal diseases. J Clin Periodontol 1986;13:905-11.  Back to cited text no. 3
Loesche WJ. Chemotherapy of dental plaque infections. Oral Sci Rev 1976;9:65-107.  Back to cited text no. 4
Loesche WJ. Role of Streptococcus mutans in human dental decay. Microbiol Rev 1986;50:353-80.  Back to cited text no. 5
Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. Microbial complexes in subgingival plaque. J Clin Periodontol 1998;25:134-44.  Back to cited text no. 6
Marsh PD. Microbial ecology of dental plaque and its significance in health and disease. Adv Dent Res 1994;8:263-71.  Back to cited text no. 7
Marsh PD. Are dental diseases examples of ecological catastrophes? Microbiology 2003;149(Pt 2):279-94.  Back to cited text no. 8
Marsh PD, Martin MV. Oral Microbiology. 5th ed. Edinburgh: Churchill Livingstone; 2009.  Back to cited text no. 9
Power M, Power ME, Tilman D, Estes JA, Menge BA, Bond WJ. Challenges in the quest for keystones. Bioscience 1996;46:609-0.  Back to cited text no. 10
Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: Keystones, pathobionts, and host response. Trends Immunol 2014;35:3-11.  Back to cited text no. 11
Hajishengallis G, Darveau RP, Curtis MA. The keystone-pathogen hypothesis. Nat Rev Microbiol 2012;10:717-25.  Back to cited text no. 12
Hajishengallis G, Lambris JD. Microbial manipulation of receptor crosstalk in innate immunity. Nat Rev Immunol 2011;11:187-200.  Back to cited text no. 13
Gemmell E, Walsh LJ, Savage NW, Seymour GJ. Adhesion molecule expression in chronic inflammatory periodontal disease tissue. J Periodontal Res 1994;29:46-53.  Back to cited text no. 14
Darveau RP. The oral microbial consortium's interaction with the periodontal innate defense system. DNA Cell Biol 2009;28:389-95.  Back to cited text no. 15
Darveau RP, Hajishengallis G, Curtis MA. Porphyromonas gingivalis as a potential community activist for disease. J Dent Res 2012;91:816-20.  Back to cited text no. 16
Darveau RP. Periodontitis: A polymicrobial disruption of host homeostasis. Nat Rev Microbiol 2010;8:481-90.  Back to cited text no. 17
Darveau RP, Belton CM, Reife RA, Lamont RJ. Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis. Infect Immun 1998;66:1660-5.  Back to cited text no. 18
Imamura T. The role of gingipains in the pathogenesis of periodontal disease. J Periodontol 2003;74:111-8.  Back to cited text no. 19
Chow J, Mazmanian SK. A pathobiont of the microbiota balances host colonization and intestinal inflammation. Cell Host Microbe 2010;7:265-76.  Back to cited text no. 20
Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: The polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol 2012;27:409-19.  Back to cited text no. 21
Hajishengallis G, Lamont RJ. Breaking bad: Manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol 2014;44:328-38.  Back to cited text no. 22
Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe 2011;10:497-506.  Back to cited text no. 23
Slots J. Human viruses in periodontitis. Periodontol 2000 2010;53:89-110.  Back to cited text no. 24


  [Table 1]


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