Periodontitis: a host‐mediated disruption of microbial homeostasis. Unlearning learned concepts

New concepts evolve when existing ones fail to address known factors adequately or are invalidated by new evidence. For decades periodontitis has been considered to be caused by specific bacteria or groups of bacteria and, accordingly, treatment protocols have largely been based on anti‐infective therapies. However, close inspection of current data leads one to question whether these bacteria are the cause or the result of periodontitis. Good evidence is emerging to suggest that it is indeed the host response to oral bacteria that leads to the tissue changes noted in gingivitis. These changes lead to an altered subgingival environment that favors the emergence of ‘periodontal pathogens’ and the subsequent development of periodontitis if the genetic and external environmental conditions are favorable for disease development. Thus, it seems that it is indeed the initial early host‐inflammatory and immune responses occurring during the development of gingivitis, and not specific bacteria or their so‐called virulence factors, which determine whether periodontitis develops and progresses. In this review we consider these concepts and their potential to change the way in which we view and manage the inflammatory periodontal diseases.     

Periodontitis and angular alveolar lesions: a critical distinction

Modern anthropologic and epidemiologic studies reveal that the incidence of periodontitis is low in both ancient and modern populations. The distribution of plaque and gingivitis has little or no correlation with the distribution of pathologic alveolar bone loss or with periodontitis. The assumption that a distance from cementoenamel junction to alveolar crest (CEJ-AC distance) greater than 2 mm equates with disease overlooks the interrelationship between the CEJ-AC distance and continuous eruption in compensation for tooth wear and growth of the lower face height. Anatomic, physiologic, and pathologic factors increasing CEJ-AC distances are reviewed. Where horizontal periodontitis does result from gingivitis, it is usually of minimal significance and probably occurs when the host defenses have been diminished by environmental factors commonly associated with other chronic diseases. A pulpal-alveolar explanation for localized angular alveolar lesions better fits the clinical features of this form of periodontal bone loss than does the conventional hypothesis of primary periodontal infection by specific oral bacteria.     

牙周炎和慢性阻塞性肺疾病间共同危险因素及相关机制研究进展

慢性阻塞性肺疾病和牙周病两者都是感染引起的慢性炎症反应性疾病,两者的临床表现均涉及结缔组织的破坏.该文就两者的流行病学情况、共同危险因素、相关的生物学机制的研究进展进行综述.文献复习结果表明牙周炎与慢性阻塞性肺疾病两者之间可相互影响,感染细菌同源性,炎症因子和中性粒细胞都参与了两种疾病的过程,两者的共同危险因素有年龄增...     

Cytokine gene expression in chronic periodontitis

Background: Cytokines play an important rôle in controlling inflammatory processes and tissue homeostasis. Periodontitis, as any other chronic inflammatory disease, results from a disarrangement of host factors, mainly cytokines and the initiating agent. Modulation of the cytokines is not only controlled by the host but also by infecting bacteria and their products. Aim: In the present study, we examined the cytokine mRNA expression profiles in six patients, each presenting sites affected with (1) severe progressive periodontitis, (2) chronic, but stable periodontal lesions, and (3) with healthy sites. Analysis using a quantitative RT‐PCR included IFN‐γ, IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, and TNF‐α. Material and Methods: 6 patients with chronic periodontitis were following treatment observed for a period of six years for local sites staying healthy, local sites with periodontal pathology but without signs of progression of attachment loss and sites with verified progression were biosied. The biopsies were lyzed and analyzed for levels of cytokine mRNAs. Results: Results revealed considerable variation not only between patients, but also between individual sites. Each patient’s site has thus to be looked at as an independent entity. Conclusions: The local action of cytokines, which is heavily dependent on recruitment, interaction and activation of immunocompetent cells can explain the site‐specific nature of cytokine expression. Cytokine data from individual sites together with the local clinical status and data from the literature demonstrate the complexity of periodontal disease pathogenesis. To gain insight to specific mechanisms further studies are needed.     

Association of the polymorphisms in promoter and intron regions of the interleukin-4 gene with chronic periodontitis in a Turkish population

Objectives. The etiology of periodontitis is related to the interaction between micro-organisms and host responses. Host modifying factors, such as genetic predisposition, may increase the severity of periodontitis. Recent works have shown that the levels of cytokine expression are regulated by genetic polymorphisms, and that these variations can interfere with progression of the disease. This study therefore aimed to evaluate whether interleukin (IL) 4 gene polymorphisms are associated with severe generalized chronic periodontitis. Material and Methods. Seventy-five severe generalized chronic periodontitis patients and 73 healthy subjects were examined. Blood samples were taken and genomic DNA was amplified by polymerase chain reaction (PCR). Identification of 70 base-pair repeat polymorphisms in intron 2 and C→T polymorphisms at ?590 position of the promoter region was performed through PCR-restriction fragment length polymorphism (RFLP). Results. No significant differences were found in the allele and genotype frequencies between the control and periodontitis group. Conclusion. The IL-4 polymorphisms were not related to severe generalized chronic periodontitis in a Turkish population.     

Bacterial invasion and persistence: critical events in the pathogenesis of periodontitis?

Periodontitis is chronic inflammation of the periodontium caused by the host's inflammatory response to plaque biofilm, which destroys tooth‐supporting soft and hard tissues. Periodontitis is a complex disease that involves interactions among three main features – microbial challenge, the host immune response, and environmental and genetic risk factors – in its pathogenesis. Although periodontitis has been regarded as the result of hyperimmune or hyperinflammatory responses to plaque bacteria, recent studies indicate that periodontal pathogens are rather poor activators and/or suppressors of the host immune response. This raises the question of how periodontal pathogens cause inflammation. To resolve this issue, in the present review we propose that bacterial invasion into gingival tissue is a key event in the initiation of periodontitis and that the persistence of these bacteria within host tissue results in chronic inflammation. In support of this hypothesis, we present the ways in which microbial, environmental and genetic risk factors contribute to bacterial invasion. It is hoped that the current model will instigate active discussion and new research to complete the puzzle of this complex disease process.     

Periodontitis is an inflammatory disease of oxidative stress: We should treat it that way

Periodontitis is a highly prevalent disease. As it progresses, it causes serious morbidity in the form of periodontal abscesses and tooth loss and, in the latter stages, pain. It is also now known that periodontitis is strongly associated with several nonoral diseases. Thus, patients with periodontitis are at greater risk for the development and/or exacerbation of diabetes, chronic obstructive pulmonary disease, and cardiovascular diseases, among other conditions. Although it is without question that specific groups of oral bacteria which populate dental plaque play a causative role in the development of periodontitis, it is now thought that once this disease has been triggered, other factors play an equal, and possibly more important, role in its progression, particularly in severe cases or in cases that prove difficult to treat. In this regard, we allude to the host response, specifically the notion that the host, once infected with oral periodontal pathogenic bacteria, will mount a defense response mediated largely through the innate immune system. The most abundant cell type of the innate immune system – polymorphonuclear neutrophils – can, when protecting the host from microbial invasion, mount a response that includes upregulation of proinflammatory cytokines, matrix metalloproteinases, and reactive oxygen species, all of which then contribute to the tissue damage and loss of teeth commonly associated with periodontitis. Of the mechanisms referred to here, we suggest that upregulation of reactive oxygen species might play one of the most important roles in the establishment and progression of periodontitis (as well as in other diseases of inflammation) through the development of oxidative stress. In this overview, we discuss both innate and epigenetic factors (eg, diabetes, smoking) that lead to the development of oxidative stress. This oxidative stress then provides an environment conducive to the destructive processes observed in periodontitis. Therefore, we shall describe some of the fundamental characteristics of oxidative stress and its effects on the periodontium, discuss the diseases and other factors that cause oxidative stress, and, finally, review potentially novel therapeutic approaches for the management (and possibly even the reversal) of periodontitis, which rely on the use of therapies, such as resveratrol and other antioxidants, that provide increased antioxidant activity in the host.     

Contemporary approaches for identifying individual risk for periodontitis

Key breakthroughs in our understanding of the etiology and principles of predictable treatment of patients with chronic periodontitis first emerged in the late 1960s and carried on into the mid‐1980s. Unfortunately, some generalizations of the evidence led many to believe that periodontitis was a predictable result of exposure to bacterial plaque accumulations over time. For a brief period, the initial plaque concept was translated by some to implicate specific bacterial infections, with both concepts (plaque exposure and specific infection) being false assumptions that led to clinical outcomes which were frustrating to both the clinician and the patient. The primary misconceptions were that every individual was equally susceptible to periodontitis, that disease severity was a simple function of magnitude of bacterial exposure over time, and that all patients would respond predictably if treated based on the key principles of bacterial reduction and regular maintenance care. We now know that although bacteria are an essential initiating factor, the clinical severity of periodontitis is a complex multifactorial host response to the microbial challenge. The complexity comes from the permutations of different factors that may interact to alter a single individual's host response to challenge, inflammation resolution and repair, and overall outcome to therapy. Fortunately, although there are many permutations that may influence host response and repair, the pathophysiology of chronic periodontitis is generally limited to mild periodontitis with isolated moderate disease in most individuals. However, approximately 20%‐25% of individuals will develop generalized severe periodontitis and probably require more intensive bacterial reduction and different approaches to host modulation of the inflammatory outcomes. This latter group may also have serious systemic implications of their periodontitis. The time appears to be appropriate to use what we know and currently understand to change our approach to clinical care. Our goal would be to increase our likelihood of identifying those patients who have a more biologically disruptive response combined with a more impactful microbial dysbiosis. Current evidence, albeit limited, indicates that for those individuals we should prevent and treat more intensively. This paper discusses what we know and how we might use that information to start individualizing risk and treat some of our patients in a more targeted manner. In my opinion, we are further along than many realize, but we have a great lack of prospective clinical evidence that must be accumulated while we continue to unravel the contributions of specific mechanisms.     

Diagnostic and prognostic tests for oral diseases: practical applications

Dental caries and periodontitis are initiated by specific bacteria and modified by host and environmental factors. Individuals have great differences in their rates of disease progression, but a small set of risk factors, such as smoking and diabetes, can distinguish patients at high risk for more severe disease. The application of information about factors that influence disease can be used to improve disease prevention and management. Knowledge of when specific information may be valuable should lead to the optimal management of individual patients. The use of diagnostic and prognostic tests and their application to the assessment and management of dental caries and periodontitis are the focus of this review.     

Principles of aetiology and pathogenesis governing the treatment of periodontal disease

Modern periodontal therapy is based on the fundamental realization that accumulation of bacterial plaque at the gingival margin causes the incipient lesion in periodontal disease. Without interference, most lesions will progress to involve deeper parts of the periodontium. Recent research has revealed that dental plaque comprises a multitude of bacteria in various combinations with a variety of pathogenic potentials, that supragingival plaque is significantly different from the subgingival variety and that particular bacterial species are associated with different periodontal disease states. However, studies have not yet clearly defined a group of bacteria, much less one species, that is responsible for the different forms of periodontal disease. Therefore, the concept of specific pathogenesis is still not ready for clinical application in the prevention and treatment of these diseases, and dental plaque must be dealt with as an entity. Investigators have failed to demonstrate local or systemic factors, other than local aggregates of micro-organisms, that cause gingivitis and periodontitis. As in any other infections, the pathological events and final outcome are determined by the relationship between the microflora and host resistance. Presently, there are no known means by which the host factors can be manipulated to enhance the defense of the periodontium. Therefore, the only rationale for the clinical management of periodontal diseases is to interfere with the microbiological events. Since it is known that gingivitis precedes periodontitis, the only useful approach to preventing the development of periodontitis is to control gingivitis. The treatment of moderate and severe periodontitis also focuses on the elimination of subgingival bacteria and inhibition of recolonization. The target for this is the root surface, which must be detoxified. Surgical elimination of periodontal pockets is still a valid approach to the treatment of the advanced periodontal lesion but only in so far as it provides access to the subgingival accumulations of plaque. The key to success in periodontal therapy is to prepare the tooth surfaces in such a way as to make them biologically acceptable to the gingival tissues. This may be achieved with or without gaining surgical access.     

Update on human cytomegalovirus in destructive periodontal disease

AIM: Human cytomegalovirus (HCMV), a herpesvirus, is discussed in this review as it relates to destructive periodontal disease in humans. RESULTS: HCMV genomic sequences, detected by polymerase chain reaction identification, occur with elevated frequency in severe adult periodontitis, localized and generalized aggressive (juvenile) periodontitis, Papillon-Lefèvre syndrome periodontitis, acute necrotizing ulcerative gingivitis, and periodontal abscesses. DISCUSSION: Herpesviruses establish lifelong persistent infections. HCMV infection involves an asymptomatic latent phase interrupted by periods of recrudescence where viral replication and possibly clinical disease become manifest. HCMV reactivation is triggered by a number of immunosuppressive factors, some of which have been shown also to be risk factors/indicators of periodontitis. HCMV periodontal infection may cause release of tissue-destructive cytokines, overgrowth of pathogenic periodontal bacteria, and initiation of cytotoxic or immunopathologic events. CONCLUSIONS: A growing body of data supports the concept that HCMV contributes to severe types of periodontal disease. HCMV infection of the periodontium may alter the immune control of resident microorganisms and be important in a multistage pathogenesis of periodontitis involving viral activation, periodontopathic bacteria, and host immune responses. Understanding the significance of HCMV and other herpesviruses in the development of periodontal disease may have important therapeutic implications. Vaccines against HCMV, which are in various stages of development, need to be evaluated for their ability to decrease the incidence of destructive periodontal disease.     

Current concepts in periodontal pathogenesis

Periodontal research over the last 40 years has been remarkably prolific. We now understand that severe periodontitis affects approximately 10-15% of the population (representing a large number of individuals in the UK) and gingivitis and mild periodontitis affect a majority of people. Microbiological research has identified some of the key pathogens that are implicated in periodontal disease. Plaque bacteria exist in biofilms, which have evolved to protect individual organisms within the subgingival bacterial community. For this reason, root surface instrumentation (RSI) remains the cornerstone of periodontal treatment, and is necessary to disrupt the subgingival biofilm mechanically and reduce the bacterial bioburden. Although bacteria are necessary for periodontal disease to occur, a susceptible host is also required. The immune-inflammatory response that develops in the gingival and periodontal tissues in response to the chronic presence of plaque bacteria results in destruction of structural components of the periodontium leading, ultimately, to the clinical signs of periodontitis. The nature of the host response is determined primarily by genetic factors and environmental and acquired factors such as smoking. The host response is essentially protective in nature, but both under-activity (hypo-responsiveness) and over-activity (hyper-responsiveness) of aspects of the host response can result in enhanced tissue destruction. The purpose of this paper is to review current thinking in periodontics with special reference to periodontal epidemiology, microbiology, and pathogenesis.     

单核苷酸多态性与慢性牙周炎相关关系的研究进展

单核苷酸多态性(SNP)是指基因组中特异位点单个核苷酸变异形成的遗传标记,慢性牙周炎是发生在牙周支持组织的一种多因素导致的慢性感染性疾病,二者间存在着密切的相关关系,其研究主要集中于在免疫系统识别、清除细菌和组织破坏过程或代谢机制中发挥作用的细胞因子、细胞膜受体、趋化因子和酶等编码基因的多态性等.本文就白细胞介素、肿瘤坏死因子、Fcγ受体、维生素D受体和基质金属蛋白酶五大基因家族SNP与慢性牙周炎易患性相关关系的研究进展作一综述,从SNP的角度寻求慢性牙周炎易患性诊断的依据.     

Microbiology of aggressive periodontitis

For decades, Aggregatibacter actinomycetemcomitans has been considered the most likely etiologic agent in aggressive periodontitis. Implementation of DNA‐based microbiologic methodologies has considerably improved our understanding of the composition of subgingival biofilms, and advanced open‐ended molecular techniques even allow for genome mapping of the whole bacterial spectrum in a sample and characterization of both the cultivable and not‐yet‐cultivable microbiota associated with periodontal health and disease. Currently, A. actinomycetemcomitans is regarded as a minor component of the resident oral microbiota and as an opportunistic pathogen in some individuals. Its specific JP2 clone, however, shows properties of a true exogenous pathogen and has an important role in the development of aggressive periodontitis in certain populations. Still, limited data exist on the impact of other microbes specifically in aggressive periodontitis. Despite a wide heterogeneity of bacteria, especially in subgingival samples collected from patients, bacteria of the red complex in particular, and those of the orange complex, are considered as potential pathogens in generalized aggressive periodontitis. These types of bacterial findings closely resemble those found for chronic periodontitis, representing a mixed polymicrobial infection without a clear association with any specific microorganism. In aggressive periodontitis, the role of novel and not‐yet‐cultivable bacteria has not yet been elucidated. There are geographic and ethnic differences in the carriage of periodontitis‐associated microorganisms, and they need to be taken into account when comparing study reports on periodontal microbiology in different study populations. In the present review, we provide an overview on the colonization of potential periodontal pathogens in childhood and adolescence, and on specific microorganisms that have been suspected for their role in the initiation and progression of aggressive forms of periodontal disease.     

The paradox of painless periodontal disease

Periodontal diseases, primarily gingivitis and periodontitis, are characterised by progressive inflammation and tissue destruction. However, they are unusual in that they are not also accompanied by the pain commonly seen in other inflammatory conditions. This suggests that interactions between periodontal bacteria and host cells create a unique environment in which the pro‐algesic effects of inflammatory mediators and factors released during tissue damage are directly or indirectly inhibited. In this review, we summarise the evidence that periodontal disease is characterised by an accumulation of classically pro‐algesic factors from bacteria and host cells. We then discuss several mechanisms by which inflammatory sensitisation of nociceptive fibres could be prevented through inactivation or inhibition of these factors. Further studies are necessary to fully understand the molecular processes underlying the endogenous localised hypoalgesia in human periodontal disease. This knowledge might provide a rational basis to develop future therapeutic interventions, such as host modulation therapies, against a wide variety of other human pain conditions.     

Antibody reactive with Porphyromonas gingivalis hemagglutinin in chronic and generalized aggressive periodontitis

BACKGROUND: Porphyromonas gingivalis, a black-pigmented, gram-negative anaerobe, is found in periodontitis lesions and its presence in subgingival plaque significantly increases the risk for periodontitis. We have previously shown that patients with aggressive forms of periodontitis that are seropositive for P. gingivalis have less attachment loss than those that are seronegative. This suggests that antibody reactive with antigens of P. gingivalis may be protective and decrease disease severity and extent. Recent studies in the murine abscess model and in the host antibody response in chronic periodontitis patients suggest that antibody reactive with P. gingivalis hemagglutinin may be an important protective antibody response. OBJECTIVES: In this study, we tested the hypothesis that there was a significant relationship between antibody reactive with P. gingivalis hemagglutinin and measures of periodontal attachment loss. METHODS: We determined the immunoglobulin G (IgG) antibody concentration reactive with recombinant P. gingivalis hemagglutinin in 117 chronic periodontitis and 90 generalized aggressive periodontitis patients. We also determined the IgG subclass distribution for antibody reactive with P. gingivalis hemagglutinin. RESULTS AND CONCLUSIONS: We found IgG reactive with P. gingivalis hemagglutinin in both chronic periodontitis and generalized aggressive periodontitis patients. Most of this IgG antibody was of the IgG1 and IgG3 subclasses. Antibody reactive with P. gingivalis hemagglutinin, however, did not have a significant relationship with measures of periodontal attachment loss.     

Discuss the role of microorganisms in the aetiology and pathogenesis of periapical disease

The literature indicates that microorganisms have a critical role in the aetiology and pathogenesis of apical periodontitis. The advancement in microbiological study methods has allowed for the identification of newer species associated with the disease process. At our current understanding, however, the exact roles of specific microorganisms in apical periodontitis are not fully understood but the poly‐microbial aetiology of the disease appears to be supported by the literature. The endodontic microbiota is comprised of a subset of microbiota present in the oral cavity, consisting of predominantly anaerobic bacterial species, some fungal and viral species. The pathogenesis of apical periodontitis is essentially the result of a complex interplay between bacterial and host factors, giving rise to a range of presentations depending on the balance of the interaction. The role of endodontic microbiota in the initiation and persistence of apical periodontitis means that the mainstay of endodontic treatment is the elimination of such bacteria. A challenge to the resolution of apical periodontitis after treatment lies in the inadequacy of treatment protocol in completely eradicating the pathogenic species and the inherent ability of certain species to survive the treatment. This issue should be the focus of future research as we continually search for more predictable treatment methods of achieving the resolution of apical periodontitis.     

Virulence factors of the oral spirochete Treponema denticola

There is compelling evidence that treponemes are involved in the etiology of several chronic diseases, including chronic periodontitis as well as other forms of periodontal disease. There are interesting parallels with other chronic diseases caused by treponemes that may indicate similar virulence characteristics. Chronic periodontitis is a polymicrobial disease, and recent animal studies indicate that co-infection of Treponema denticola with other periodontal pathogens can enhance alveolar bone resorption. The bacterium has a suite of molecular determinants that could enable it to cause tissue damage and subvert the host immune response. In addition to this, it has several non-classic virulence determinants that enable it to interact with other pathogenic bacteria and the host in ways that are likely to promote disease progression. Recent advances, especially in molecular-based methodologies, have greatly improved our knowledge of this bacterium and its role in disease.     

Cementum hypoplasia in teeth affected by juvenile periodontitis

The cemental surface of teeth affected by juvenile periodontitis was examined using scanning electron microscopy. Molars affected by chronic marginal periodontitis and healthy molars were included as controls. The entire mesial root of teeth affected by juvenile periodontitis showed extensive areas of cementum hypoplasia with exposed dentinal tubules. The hypoplasias were found also on the infracrestal part of the root indicating that they had not been caused by exposure to the oral environment or by any treatment. Cementum hypoplasias were not found in any teeth from the control material. The impaired periodontal attachment in the hypoplasia may facilitate penetration by the special motile bacteria which have been found in plaque from teeth with juvenile periodontitis. Based on the findings in the present study and the hereditary background of juvenile periodontitis it was suggested that development of the disease is initiated by a hereditary developmental disturbance of the cementum.