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Periodontitis: a polymicrobial disruption of host homeostasis

Key Points

  • Periodontitis is intimately associated with a characterized polymicrobial dental-plaque community. However, the species and mechanisms that result in disease remain unclear.

  • The main protective mechanism of the periodontium is the orchestrated expression of select innate host defence mediators. These mediators reduce the microbial load on the epithelial-cell surface by both neutralization and bacterial killing.

  • The main mechanism of bone loss in periodontitis seems to be mediated by the host response to a unique microbial consortium. However, most of the bacteria found in the dental-plaque biofilm are capable of initiating inflammatory cytokine responses, rendering identification of key indicators of disease difficult.

  • Examination of gingival crevicular fluid from clinically healthy sites revealed that this fluid contains cytokines that may induce inflammation. However, the levels of these cytokines in healthy sites are lower than levels in diseased sites, indicating that a disruption of host homeostasis contributes to disease.

  • Extensive analysis of dental-plaque bacteria associated with disease has revealed three bacterial species that display strong associations both with each other and diseased sites. Evidence indicates that these bacteria, designated the 'red-complex' species, may interfere with the protective barrier of the host innate defence response.

  • Red-complex bacteria maybe key species in the pathogenic dental-plaque biofilm. By modulating the innate host defence barrier, they facilitate the growth of other members of the dental-plaque biofilm. The increase in the number and types of bacterial species that occupy the gingival crevice present multiple opportunities to disrupt host homeostasis programmes.

  • Physical removal of the dental-plaque biofilm remains the most effective treatment. However, vaccine strategies targeting red-complex bacteria have also shown efficacy in animal models of disease. The ability to attenuate bone loss by the inhibition of a single bacterial species is consistent with the key species concept.

  • A novel pro-resolving mediator shows promise as an effective periodontitis treatment in pre-clinical studies. A compound that restores host homeostasis is consistent with the theory that an important component of the disease is disruption of host homeostasis programmes.

Abstract

Periodontitis, or gum disease, affects millions of people each year. Although it is associated with a defined microbial composition found on the surface of the tooth and tooth root, the contribution of bacteria to disease progression is poorly understood. Commensal bacteria probably induce a protective response that prevents the host from developing disease. However, several bacterial species found in plaque (the 'red-complex' bacteria: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) use various mechanisms to interfere with host defence mechanisms. Furthermore, disease may result from 'community-based' attack on the host. Here, I describe the interaction of the host immune system with the oral bacteria in healthy states and in diseased states.

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Figure 1: The effects of periodontitis.
Figure 2: Transit of neutrophils through periodontal tissue.
Figure 3: Microbial alteration of bone homeostasis leads to localized bone loss.
Figure 4: Porphyromonas gingivalis, a member of the red-complex bacteria, inhibits innate host defence functions in gingival epithelium.

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Acknowledgements

The author thanks M. Curtis for critical review of the manuscript, M. Thomashow and F. Roberts for fruitful discussions and C. Zenobia for help with the figures. He also thanks the past and present members of his lab and department for continued inspiring conversations. The editorial assistance of N. Balch is greatly appreciated. Work in the author's laboratory is supported by the National Institute of Dental and Craniofacial Research.

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DATABASES

Entrez Genome

Treponema denticola

Entrez Genome Project

Aggregatibacter actinomycetemcomitans

Macaca fascicularis

Porphyromonas gingivalis

Tannerella forsythia

FURTHER INFORMATION

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Glossary

Periodontium

The epithelial, connective and bone tissues that both surround and support the teeth. The word comes from the Greek terms 'peri', meaning 'around', and -'odons', meaning 'tooth'.

Dental plaque

A polymicrobial biofilm community that builds up on the surface of the tooth and tooth root. Plaque can also become mineralized and form a calculus.

Microbial-shift disease

A disease caused by a decrease in the number of beneficial symbionts and/or an increase in the number of pathogens. This concept is also known as dysbiosis.

Junctional epithelium

A specialized epithelium located at the interface between the gingival sulcus, which is populated with bacteria, and the periodontal soft and mineralized connective tissues. It connects the tooth surface to the host tissue.

Germ-free mice

Mice that are completely devoid of bacteria. They are generated by sterile Caesarean section, raised aseptically in an isolator with sterile filtered air and housed using sterile food, water and bedding. Germ-free mice are distinct from specific-pathogen-free (SPF) mice, which are devoid of only known mouse pathogens and still contain intestinal bacteria.

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Darveau, R. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol 8, 481–490 (2010). https://doi.org/10.1038/nrmicro2337

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