Kilian M, Chapple IL, Hannig M The oral microbiome – an update for oral healthcare professionals. Br Dent J. 2016; 221:657-666 https://doi.org/10.1038/sj.bdj.2016.865
Raina JB, Eme L, Pollock FJ, Spang A, Archibald JM, Williams TA Symbiosis in the microbial world: from ecology to genome evolution. Biol Open. 2018; 7 https://doi.org/10.1242/bio.032524
Hajishengallis G Interconnection of periodontal disease and comorbidities: evidence, mechanisms, and implications. Periodontol 2000. 2022; 89:9-18 https://doi.org/10.1111/prd.12430
Preda VG, Săndulescu O Communication is the key: biofilms, quorum sensing, formation and prevention. Discoveries (Craiova). 2019; 7 https://doi.org/10.15190/d.2019.13
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Miller WDPhiladelphia, PA: SS White Dental Manufacturing Co; 1890
Plaque biofilm in periodontitis: past, present and future Maryam Alshamsi Emily Ming-Chieh Lu Dental Update 2025 52:5, 332-338.
Authors
MaryamAlshamsi
BDS, MClinDent Perio, EFP Board Certified, Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London.
BDS, MClinDent Perio, EFP Board Certified, Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London.
Periodontitis is caused by an inappropriate activation of the host response to plaque biofilm. The accumulation of plaque biofilm leads to dysbiosis, that is, an imbalance in microbial community composition and function, which drives tissue destruction. Historical plaque hypotheses provide a foundational understanding of the role of plaque in the pathogenesis of periodontitis {AQ – edit OK?}. More contemporary theories emphasize how dysbiosis can trigger an exaggerated host response, leading to tissue destruction and periodontitis. As periodontitis is a biofilm-related disease, clinicians should be aware of the importance of regular mechanical disruption of plaque biofilm in managing periodontitis.
CPD/Clinical Relevance:
Practitioners should aware of the importance of regular professional mechanical plaque removal, which is integral to the overall management of periodontal disease.
Article
In the complex ecosystem of the human body, a diverse array of micro-organisms inhabits various anatomical regions, including the skin, respiratory tract, urogenital tract and gastrointestinal tract, which includes the oral cavity. Collectively known as the microbiota, these micro-organisms play a crucial role in maintaining health through their interactions with the immune system.1
The oral microbiota accounts for a significant component of the human microbiota, comprising more than 700 distinct species, including bacteria, fungi, viruses and protozoa. The oral cavity hosts the second most diverse microbiota in the human body.2
These micro-organisms inhabit specific micro-environments within the oral cavity, such as the teeth, gingival sulcus, tongue, hard and soft palates, and tonsils. Each of these niches has a unique local environment that drives the composition and behaviour of the microbial communities, allowing them to exist either in a planktonic form or as components of complex polymicrobial biofilms, such as plaque biofilm.
In health, the oral microbiota and the host are in a symbiotic relationship where both parties benefit from the interactions.3 A balanced and diverse microbiome supports a strong defence against infection and helps maintain overall homeostasis.1,3 A disruption to this balance, leading to dysbiosis, can have significant consequences.
Dysbiosis occurs when there is a decrease in beneficial microbes or an increase in pathogenic micro-organisms, leading to an imbalance in the microbial community and triggering inappropriate activation of the host's defence mechanisms.
This imbalance between the oral microbiome and host immune system is linked to periodontitis, as well as various systemic diseases, including cardiovascular disease, diabetes, Alzheimer's disease, cancer, rheumatoid arthritis, chronic kidney disease, inflammatory bowel disease and respiratory diseases.4,5
The interactions between the host and the oral microbiota within plaque biofilm play a pivotal role in the transition from gingival health to periodontal disease. Therefore, the aims of this review are: to provide an up-to-date summary of the role of plaque biofilm in the aetiology of periodontal disease; and to examine historical and contemporary plaque hypotheses that have been proposed to explain the pathogenesis of periodontitis.
Dental biofilm
Dental biofilm, commonly referred to as dental plaque, is a persistent layer consisting of diverse micro-organisms within an extracellular polymer matrix. This biofilm forms continuously and naturally on surfaces within the oral cavity, including teeth, dental implants and dentures.
Micro-organisms contribute to about 70% of biofilms’ dry weight, with the rest comprising a matrix of polysaccharides, salivary proteins and glycoproteins.
The matrix within the biofilm serves multiple functions, such as providing protection, facilitating the adhesion of micro-organisms to surfaces, promoting stability of the biofilm structure and supplying nutrients necessary for microbial growth and survival.6
The process of dental biofilm formation confers benefits to the host by protecting against exogenous colonization by pathogenic bacteria. Biofilm formation creates a microbial environment that prevents pathogenic bacteria from adhering to tooth surfaces and accessing nutrients, thereby reducing the potential for infections. Additionally, a well-formed biofilm can help maintain a balanced microbial community, which plays a role in preventing pathogenic overgrowth.7,8
However, failure to regularly disrupt the accumulation of dental biofilm through proper oral hygiene practices can lead to gingivitis, an inflammatory condition characterized by redness and swelling of the gingival tissue without any periodontal loss of attachment.9
The development of plaque-induced gingivitis was demonstrated in a landmark experimental gingivitis study, where participants who abstained from oral hygiene practices predictably developed gingivitis.10
Therefore, dental plaque biofilm is recognized as the primary aetiological factor for the development of gingival inflammation, and, in susceptible individuals, this can progress to periodontitis.
The formation of the biofilm begins with the development of the salivary pellicle, a thin film comprising salivary glycoproteins and gingival crevicular fluid that adheres to tooth surfaces through arbitrary or chemical interactions. Initial attachment occurs between bacterial cells and the salivary pellicle, leading to the formation of a firmly adherent band of organisms on enamel or root surfaces. This attachment involves reversible, weak, long-range physico-chemical interactions.11
The initial colonization of the pellicle consists mainly of Gram-positive aerobic cocci and rods, such as streptococci and actinomyces, which are linked to gingival health.11 As these early colonizers establish themselves, they facilitate the subsequent attachment of intermediate and late colonizers onto existing attached organisms by Gram-negative anaerobes, which include Fusobacterium nucleatum, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and Aggregatibacter actinomycetemcomitans.12
The adhesion properties of these bacteria involve interactions between bacterial adhesins and host receptors that are crucial for bacterial succession within the biofilm aggregate; the late colonizers will eventually substitute the early colonizers in promoting the maturation of plaque.13
As the biofilm matures, it becomes more structured, with distinct microbial communities and increased resistance to disruption and antimicrobial agents. This maturation process is critical to the biofilm's ability to cause disease.
Pathogenic micro-organisms can replicate within the biofilm, evading host immune responses owing to distinct virulence factors. Moreover, micro-organisms within the biofilm exhibit greater resistance to eradication compared to their freefloating counterparts owing to their protective matrix and cooperative interactions and can evade immune and antimicrobial agents.14
Therefore, the use of systemic antimicrobial agents alone in the management of periodontal disease is contraindicated. They should be used only in conjunction with mechanical disruption of the biofilm through professional mechanical plaque removal.15
Historical plaque theories
Non-specific plaque hypothesis
In 1890, Miller proposed the non-specific plaque hypothesis (NSPH), which established a link between dental plaque and the development of periodontal disease. The NSPH suggests that periodontal disease arises from the overall microbial composition of dental plaque rather than from any particular bacterium or virulence factor.
In particular, this hypothesis proposes that all bacteria within the dental biofilm have an equal potential to induce disease, and that the host's response to the plaque is proportionate to the plaque mass, irrespective of the virulence of individual bacteria.16
The strength of the NSPH lies in its emphasis on the collective action of the entire microbial community within dental plaque, which simplifies the understanding of disease mechanisms by attributing this action to the overall microbial load.
This approach supports straightforward preventive measures, such as comprehensive plaque removal through good oral hygiene practices. However, the NSPH falls short by not accounting for the specific role of different bacterial species in disease progression, leading to a potential overgeneralization of treatment approaches.
Specific plaque hypothesis
The specific plaque hypothesis (SPH), introduced by Loesche in 1976, emphasized identifying specific micro-organisms associated with periodontal disease and distinguishing between the microbiomes linked with health and disease.17
According to the SPH, shifts in plaque composition from a healthy to a diseased state involve certain subgingival bacteria with greater virulence contributing to disease progression.17
The key feature of the SPH is the identification of specific pathogenic bacteria responsible for periodontal disease, which encourages a more focused diagnostic and therapeutic intervention.
However, effective targeting of specific micro-organisms is limited and the potential role of vaccinations against specific pathogens requires extensive research.19–20
The main disadvantage with the SPH is that it does not account for individuals who present with significant plaque accumulation yet do not develop severe periodontitis. The SPH views periodontal disease as an infection driven by specific pathogenic micro-organisms, with disease severity influenced by the presence or increased abundance of these specific microbes, rather than driven by aberrant host response.17
Ecological plaque hypothesis
The ecological plaque hypothesis, proposed by Marsh in 1994, suggests that changes in the composition and quantity of the oral microbiota within dental biofilm contributes to the shift from oral health to disease.8
This hypothesis proposes that alteration in microbial diversity and abundance occur due to ecological stressors, including host-related factors (such as immunodeficiencies and pregnancy) and environmental factors (such as smoking and diet).
These stressors lead to persistent inflammation and tissue breakdown, creating an environment favourable for dysbiotic microbial communities.
Consequently, there is a decline in commensal species and an increase in potentially pathogenic species within the dental biofilm.
The strength of the ecological plaque hypothesis lies in its focus on how host immune response and environmental changes within the oral cavity, such as pH and nutrient availability, influence microbial composition. This perspective provides a comprehensive understanding of disease aetiology and supports interventions that aim to restore balance in the oral microbiome.
However, the dynamic nature of microbial ecosystems can complicate the design of straightforward treatment protocols, as changes in microbial communities are influenced by a complex interplay of factors.
Contemporary concepts
Keystone pathogen model
The keystone pathogen model, proposed by Hajishengallis et al in 2012, describes how certain microbial species, despite being present in low quantities, can have a disproportionate impact on their environment.21 According to this model, these keystone pathogens disrupt the host's immune response and initiate inflammatory diseases by disturbing the balanced symbiotic microbiota, which leads to dysbiosis.21 Although these pathogens alone are insufficient to cause disease, they induce pathogenic changes in the microbiota by altering its composition, thereby contributing to disease development.
The model emphasizes the critical role of communication between keystone pathogens and commensal microbiota.21 For instance, Porphyromonas gingivalis is identified as a primary keystone pathogen that evades host defences and promotes the development of a pathogenic, dysbiotic biofilm.21 This interaction is essential for evading host immunity and driving inflammation.
The primary advantage of the keystone pathogen model is its potential for developing targeted therapeutic strategies by focusing on specific keystone pathogens, which also enhances understanding of disease mechanisms.
However, its narrow focus on individual pathogens may overlook the broader interactions between various microbial species and environmental factors that also contribute to disease progression.
Polymicrobial synergy and dysbiosis model
The polymicrobial synergy and dysbiosis (PSD) model of periodontitis, proposed by Lamont and Hajishengallis in 2015, challenges the conventional view that periodontitis is caused by specific periodontal pathogens.22 Instead, it attributes periodontitis to dysbiotic, synergistic microbiota (Figure 1).22
Figure 1. The polymicrobial synergy and dysbiosis model proposes that periodontitis is not solely caused by specific periodontal pathogens, but by dysbiotic, synergistic microbiota. This dysbiosis-driven process involves a self-perpetuating cycle of increasing dysbiosis and inflammatory bone loss, facilitated by keystone pathogens that exhibit mutually reinforcing virulence traits. Metabolically compatible organisms engage in polymicrobial synergy, allowing them to evade the host's immune response. Reproduced with kind permission of Elsevier from Lamont and Hajishengalli.22
The model emphasizes the cooperative interactions among multiple microbial species that drive dysbiosis and disease, providing a holistic view of pathogenesis. Periodontitis is seen as a result of a self-perpetuating cycle of dysbiosis and inflammatory bone loss, leading to tissue damage.22
The PSD model also emphasizes the role of keystone pathogens with mutually reinforcing virulence factors, which contribute to a microbial community exhibiting polymicrobial synergy. This synergy enables these pathogens to evade the host's immune response and exacerbate inflammation, driving the progression of periodontitis.
By highlighting these complex microbial interactions, the model supports therapies aimed at modulating the entire microbial community to restore balance, which may lead to more effective treatments.
However, it may fall short in addressing the individual variations in microbiome and host response, highlighting the need for personalized treatment.
Contemporary model
The contemporary model of periodontitis pathogenesis, proposed by Meyle and Chapple in 2015, challenges the traditional view that periodontitis is solely caused by pathogenic microflora triggering inflammation. Instead, this model suggests that dysbiosis, similar to that seen in gingivitis, begins with the host's inflammatory response.23
Failure to disrupt or remove biofilm leads to frank dysbiosis, resulting in destructive, irreversible inflammation characteristic of periodontitis.23
This model portrays periodontitis as a chronic, self-destructive condition arising from an inability to resolve excessive inflammation, highlighting a reciprocal association between periodontal biofilm and the inflammatory immune response, where the host provides essential nutrients while micro-organisms in biofilm stimulate an effective immune response in the host.23
The underlying assumption is that, in susceptible individuals, the transition from oral health to gingivitis and eventually to periodontitis is linked to the transformation of a biofilm from a health-promoting state to one exhibiting incipient dysbiosis and, ultimately, frank dysbiosis.23
Concurrently, the host's inflammatory response progresses from proportionate and pro-resolving to proportionate but non-resolving, eventually becoming disproportionate and non-resolving.23
The model's advantage lies in its comprehensive approach, integrating microbial, host and environmental factors to provide a nuanced understanding of disease progression and variability in treatment response.
However, practical implementation of treatment based on this model can be challenging owing to the need for advanced diagnostic tools and personalized treatment strategies to take account of both microbial and host-related factors.
Inflammation-mediated polymicrobial-emergence and dysbiotic-exacerbation model (IMPEDE)
Inflammation is a protective vascular and cellular response against irritants and infections that enables survival and maintains tissue homeostasis under many noxious conditions.24 A controlled, lowsurveillance inflammatory response to dental plaque can maintain tissue homeostasis and will prevent gingivitis from progressing to periodontitis.24
In line with this, the inflammation-mediated polymicrobial-emergence and dysbiotic-exacerbation (IMPEDE) model was recently proposed by Van Dyke et al in 2020. This proposal, designed to support the implementation of the 2017 World Workshop Classification of Periodontitis, underscores the critical role of inflammation in driving polymicrobial dysbiosis and the progression of periodontitis.25
The IMPEDE model recognizes five stages in the continuum from periodontal health to periodontitis (Figure 2), where disease may either be contained or progress to the next stage. These are:
Figure 2. The inflammation-mediated polymicrobial-emergence and dysbiotic-exacerbation (IMPEDE) model delineates five stages of periodontal disease progression, spanning from health through gingivitis to periodontitis. Each stage represents a pivotal point where disease can be contained or escalated. Effective control and regulation of the host immune and inflammatory response prevent the transition from gingivitis to periodontitis. Therefore, managing inflammation is crucial in halting disease progression and maintaining oral health. Conversely, dysregulated inflammation fuels disease progression, perpetuating a cycle of inflammation-mediated dysbiosis that leads to chronic inflammation and progressive periodontal tissue destruction. (Reproduced from Van Dyke et al.24)
Stage III: inflammation-mediated dysbiosis and opportunistic infection;
Stage IV: late-stage periodontitis.
The key premise of the IMPEDE model is that a controlled, low-level inflammatory response to dental biofilm can maintain tissue homeostasis and prevent the progression of gingivitis to periodontitis.25 Consequently, effective control and regulation of the host immune and inflammatory response are crucial in averting disease progression.25
Conversely, a dysregulated inflammatory response fuels disease progression, perpetuating a cycle of inflammation-mediated dysbiosis that fosters chronic inflammation and progressive destruction of periodontal tissue.
The IMPEDE model highlights the importance of targeting inflammation to disrupt this vicious cycle and mitigate the pathogenesis of periodontitis.
The model's strengths include its focus on inflammation in driving dysbiosis. However, its emphasis on inflammation and dysbiosis may sometimes overshadow other contributing factors, such as a genetic predisposition or systemic health conditions, which also play significant roles in the pathogenesis of periodontitis.
Conclusion
In summary, dental plaque biofilm is a complex microbial community that acts as the primary aetiological factor for periodontal disease by eliciting an aberrant host response.
Dysbiosis, characterized by an imbalance in both microbial composition and function within the biofilm, plays a pivotal role in disease progression.
The keystone pathogen model introduces a contemporary perspective, emphasizing the significant impact certain microbial species can exert on their environment despite their low abundance.
More recently, the IMPEDE model has shed light on the intricate interplay between inflammation and dysbiosis, elucidating how these processes synergistically drive the progressive nature of periodontitis. This model is gaining traction and appears to be one that most fittingly reflects the pathogenesis of periodontitis.
As micro-organisms within the biofilm exhibit great resistance to eradication from antimicrobial agents alone, clinicians should be aware of the importance of regular professional mechanical plaque removal, which is integral to the overall management of periodontal disease.
Persistent bacteria, if not mechanically removed from nonshedding surfaces such as teeth, can promote disease and dysbiosis.
While some bacteria exist in a state of symbiosis with the host, it remains unclear how many are required to cause of shift from health to disease. Therefore, the overall aim should be to restore and maintain the microbiome in a healthy, balanced state.
Clinicans should advise patients on lifestyle changes, such as smoking cessation and better diabetic control, to support oral health and prevent dysiosis.
Limiting antibiotic use is crucial to preventing bacterial resistance and ensuring effective management of periodontal disease.
