The Evolution of Plaque Hypotheses in Periodontal Disease Progression
Figure 10. The Evolution of Plaque Hypothesis
When Anton Von Leeuwenhoek first discovered the existence of microbes in the 17th Century, there was no way of identifying specific bacterial species. In the late 19th Century, with advances in science, several specific pathogens were identified to be associated with a variety of systemic diseases, however none were found for oral diseases despite ongoing searches. Subsequently, dental scientists believed that periodontal disease was linked with some constitutional defect in the individual.25 That time period is referred to as the ‘Golden Age of Microbiology’.
The search for specific periodontal bacteria continued beyond the mid-part of the 20th century. However, since no specific bacteria could be identified, all plaque was viewed as bad plaque. Mechanical irritants such as calculus and overhanging restorations were also thought to play a major role in the pathogenesis of periodontal disease.26 Stringent plaque control thus became the focus of periodontal therapy. This period of time was referred to as the Non-specific Plaque Hypothesis since no specific microorganisms were identified.
Discoveries in the late 1960’s and early 1970’s marked a return to the idea of a Specific Plaque Hypothesis when researchers successfully demonstrated that periodontal disease could be transmitted between hamsters.27 The specific plaque hypothesis identified a shift from predominantly gram positive aerobes to gram negative anaerobes in oral communities. Research efforts also identified specific groups of bacteria that were significantly associated with periodontitis. Socransky used DNA-DNA hybridization to identify complexes, or groups of bacteria that were thought to be major etiologic contributors to periodontal diseases. Yellow, green, blue and purple complexes were thought to be compatible with gingival health, while orange and red were associated with disease. Once it was identified that some of these bacteria could also be present in the absence of disease, additional refinement was indicated to support the specific plaque and Socransky’s Microbial Complexes concepts.28 In 1976 scientists proposed that only a few species from the total microflora were actively involved in disease and thus once again the search for a specific microbial periodontal pathogen began and treatment was aimed at the causative agent.28 That period however did not last long. In 1986 there was a return to the Non-specific Plaque Hypothesis because scientists began to suspect that the overall activity of the microflora could lead to disease by taking into account differences in virulence among the various species of bacteria.28
In 1994, researchers combined the key concepts of the earlier two hypotheses proposing that the disease was the result of an imbalance in the microflora that could be caused by ecological stress resulting in an enrichment of certain disease-related microorganisms.28 This became known as the Ecological Plaque Hypothesis and was the beginning of the concept of dysbiosis that is now in the current literature.29
More advanced bacterial profiling techniques available in the early 2000’s such as 16SrRNA-based bacterial profiling using next generation sequencing, reverse transcription-polymerase chain reaction, microarray and pyrosequencing technology, enabled the launching of the Human Microbiome project by the NIH in 2008. This project resulted in the identification of over 700 species of distinct oral microbial species with suggestions of numbers as high as 1,200-1,500.1 Of course not all 700+ species have been found to be associated with periodontal disease.
Following these discoveries made during the Human Microbiome project, the ecological plaque hypothesis was taken one step further in 2012 by Hajishengalis and colleagues30 who proposed that certain low-abundance microbes could integrate with the host immune system and remodel the microbiota thereby causing inflammatory disease. In line with earlier findings, gram negative anaerobic bacteria were most commonly found to be associated with periodontitis such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola (Red complex bacteria); Prevotella intermedia, Fusobacterium nucleatum, Parvimonas micros, Campylobacter recta, multiple species of Eubacterium, and multiple species of Bacteroides (Orange complex); Aggregatibacter actinomycetemcomitans (Green complex); and F. alocis (gram positive rod more recently identified).15,35 Of this group of bacteria, only two are considered as “keystone” microbes, P. gingivalis and F. alocis. Keystone microbes are classified as those appearing in lower numbers but who have inherent virulence factors that allow them to interact with the host innate immune system and alter a symbiotic microbiota into one that is dysbiotic.15 In addition to being keystone microbes, both P. gingivalis and F. alocis are highly virulent microbes that have a possible commensal relationship and also are able to by-pass the host immune response.15,37
This became known as the Keystone Pathogen Hypothesis.30 This hypothesis was in direct contrast to earlier beliefs that dominant species when abundant were what influenced inflammation. This new hypothesis suggested that keystone pathogens such as Porphyromonas gingivalis (P. gingivalis) triggered inflammation when they were present in “low” numbers by interfering with the innate immune system causing a shift in the host response triggering inflammation. Research began to demonstrate that commensal bacteria must be present to trigger other bacteria to cause disease.30
Although this hypothesis is the most recent and offers a plausible explanation of the significance of the microbial community when compared with patients who have periodontal disease and those who are healthy, there are still some unknowns. The problem is that keystone pathogens can be any species and some that are not necessarily pathogenic.29 Newer research has surfaced exploring what actually triggers commensal microbes to alter the symbiotic state and suspect that this alteration ultimately leads to localized inflammation, and if not controlled by the host innate immune system, is what leads to the ultimate state of dysbiosis found in periodontitis.4 This new model, proposed by Van Dyke et al. the “Inflammation-Mediated-Polymicrobial-Emergence and Dysbiotic-Exacerbation” (IMPEDE) model was designed by its authors as a subsequent follow-up to the 2017 World Workshop Classification of Periodontitis.4 It hypothesizes that initial inflammation initiated by the innate immune system in its attempt to restore symbiosis, is what ultimately leads to the dysbiosis that causes periodontitis. It also suggests that there are multiple factors that are at play such as one’s genetics, environmental factors, and host response to pathogens.5
Figure 11. SEM of mature human dental plaque demonstrating corn cob formation. Bar = 10 microns at an original magnification of 2,020.
Image courtesy of Dr. Charles Cobb. University of Missouri-Kansas City