The evolution of plaque hypotheses: The past, present, and future

Over the years, we have seen the sticky mass of bacteria that accumulate around the teeth referred to as plaque by most oral health care professionals and clients, but several other terms have surfaced, such as biofilm, plaque biofilm, oral microbiome, dysbiotic plaque, and dysbiotic plaque biofilm. It’s no wonder so many of us are confused and typically default to using “plaque” in our clinical conversations. However, one must wonder where all these names have come from and what is the correct term for this sticky mass that comprises a large, diverse community of microbes, some of which are beneficial (commensal) and necessary for our existence, while others may be harmful and disease producing.

Salme E Lavigne

How this sticky mass of microbes has been perceived over the centuries has changed significantly. There are numerous hypotheses that have been proposed since the mid-1800s to explain its connection to oral diseases (Table 1). Thus, let’s take a walk through history!

When Anton Von Leeuwenhoek first discovered the existence of microbes in the 17th century, which he referred to as “little animalcules,” ¹ it was not possible to identify specific bacterial species. In the 19th century, thanks to advances in science, several specific pathogens were found to be associated with various systemic diseases. However, no such associations were found for oral microbes. Dental scientists at that time believed that periodontal disease was linked to some constitutional defect in the individual rather than to any specific microorganism.² That particular period, from the mid-1800s to the early 1900s, was coined the “Golden Age of Microbiology”.

From the early to mid-20th century, unsuccessful attempts were made to find specific periodontal bacteria, resulting in the belief that all plaque was bad. Calculus and overhanging restorations were also thought to contribute to the pathogenesis of periodontal disease as they provided niches for harboring plaque.³ Thus, stringent plaque control became the focus of preventive oral care. Given that no specific bacteria were identified, this period in the history of dentistry was shaped by the “non-specific plaque hypothesis”.

Table 1.

The evolution of plaque hypotheses

Dates	Hypothesis	Main assumption
19th century	Golden age of microbiology	Specific pathogens are associated with systemic conditions (no oral pathogens found)
Early to mid-20th century	Non-specific plaque hypothesis	Periodontal disease is not caused by specific oral pathogens
1976	Specific plaque hypothesis	SEM technology may permit the identification of specific oral pathogens
1986	(back to) Non-specific plaque hypothesis	Overall activity of microbes could lead to disease through differences in virulence
1994	Ecological plaque hypothesis	Disease results from a microbial imbalance caused by ecological stress
2012	Keystone pathogen hypothesis	Certain low-abundance microbial pathogens cause inflammation by interfering with host immune response
2019	IMPEDE Model (Inflammation-Mediated-Polymicrobial-Emergence and Dysbiotic-Exacerbation)	Inflammation is the driver of the ultimate dysbiosis that leads to periodontitis rather than the pathogenic microbes themselves

Following the discovery of the scanning electron microscope (SEM) in the late 1960s, there was an enthusiastic return to the idea of a “specific plaque hypothesis” in the early 1970s when researchers identified spirochetes in the connective and epithelial tissues of patients with acute necrotizing ulcerative gingivitis.⁴ Since only a few species from the total microflora were confirmed to be actively involved in any particular disease, the search for a specific periodontal pathogen continued.⁵

With further scientific advances, however, there was a rapid return to the non-specific plaque hypothesis in 1986, based on a suspicion that, by taking into account differences in virulence among the various bacterial species, the overall activity of the oral microflora might be responsible for disease.⁵ Not long after, plaque was also recognized as a biofilm—a well-organized, cooperative community of microorganisms—and began to be referred to as “plaque biofilm”.

In 1994, a new hypothesis evolved when scientists combined the key concepts of the specific and non-specific plaque hypotheses to suggest that oral disease was perhaps related to a microbial imbalance (dysbiosis) caused by ecological stress that enriched certain disease-related microorganisms.⁵ This assumption became known as the “ecological plaque hypothesis” and marked the beginning of the current concept of dysbiosis.⁶

Based on findings from the 10-year Human Microbiome Project launched by the National Institutes of Health (NIH) in 2008, the “keystone pathogen hypothesis” was proposed in 2012.⁷ This hypothesis moved one step beyond the ecological stress assumption to propose that an integration of certain low-abundance microbes into the host immune system would result in a remodeling of the microbiota causing inflammatory disease. This new hypothesis was a major contrast to earlier beliefs that inflammation was influenced by a critical mass of dominant microbial species. It identified keystone pathogens such as Porphyromonas gingivalis (P. gingivalis) and Filifactor alosis (F. alosis) and suggested their presence in “low” numbers was the actual trigger for inflammation as they interfered with the innate immune system causing a shift in the host response. In support of this hypothesis, research began to demonstrate that normally commensal (beneficial) bacteria must be present to trigger other bacteria to cause disease.⁷ Although this hypothesis offers a plausible explanation for the significance of the microbial community, there are still some unknowns.

The most recent research on the oral microbiome has explored what actually triggers commensal microbes to alter the symbiotic state. The “inflammation-mediated-polymicrobial-emergence and dysbiotic-exacerbation” (IMPEDE) hypothesis suggests that the first stage of the process is the host’s innate immune response to maintain oral health or to restore symbiosis at the onset of gingivitis by producing initial inflammation. If this initial attempt by the host response is unsuccessful in restoring or maintaining a symbiotic or balanced state in the oral microbiome, then disease-producing microbes (pathobionts) tip the balance causing a dysbiosis, ultimately leading to periodontitis.⁸

WHAT DOES ALL THIS MEAN TO US?

This historical journey through the evolution of plaque hypotheses over the past 2 centuries highlights the incredible discoveries that have occurred to bring us to our current understanding of the microbial nature of oral diseases. A lot of progress has been made, particularly over the past decade thanks to findings from the Human Microbiome Project and major technological advancements, which have enabled the identification of over 700 microbial species in the oral microbiome. In addition, the knowledge gleaned from our basic understanding of biofilms and how these microbes interact with each other has resulted in new plaque hypotheses to enhance our understanding of how certain keystone pathogens are responsible for the initial tip towards a dysbiotic plaque biofilm. We are taken one step further by the new IMPEDE model, which helps us understand how initial inflammation produces the dysbiosis that leads to periodontitis rather than the pathogenic microbes themselves. This model provides us with a better understanding of how disease occurs.

These new discoveries have created a paradigm shift in how oral health professionals manage plaque biofilms, with the ultimate goal being restoration or maintenance of a state of symbiosis, which means taking care not to destroy the commensal species that are critical to our existence. These commensal microorganisms are responsible for the smooth running of our initial food digestion, play a critical role in maintaining oral homeostasis, and protect the oral cavity from disease.⁹ If this symbiotic balance is disrupted and our immune system is unable to restore symbiosis, more disease-producing microbes will ultimately overpower the beneficial species, dysbiosis of the oral microbiome will occur, and periodontal disease will ensue.

Understanding the mechanisms that cause this state of dysbiosis is integral to how we as oral health professionals can help our patients in maintaining or returning the periodontium to a symbiotic state. Traditional plaque control methods such as toothbrushing and interdental cleaning continue to be the primary tools for the disruption of plaque and maintenance of a state of balance or symbiosis. Chemical means of targeting pathogenic microbes (such as antimicrobial toothpastes and mouth rinses) without destroying beneficial species are continuously being researched and improved. The goal of patient education should now be to help them maintain a “state of symbiosis” rather than total microbial annihilation.

For more in-depth reading on this topic, visit dentalcare.com, where you will soon find a free continuing education course on the oral microbiome that I had the privilege of developing.¹⁰ As to what dental hygienists should call bacteria in the mouth when discussing at-home dental hygiene with their clients, “plaque biofilm” is the best option unless the conversation is about a disease state. In that case, we should all defer to the American Academy of Periodontology and the European Federation of Periodontology:

Periodontitis is a chronic multifactorial inflammatory disease associated with dysbiotic plaque biofilms and characterized by progressive destruction of the tooth-supporting apparatus.¹¹ [emphasis added]