Gum disease: how does P. gingivalis colonize the mouth?

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The human body is filled with friendly bacteria. However, some of these microorganisms, such as Veillonella parvula, may be too nice.

These peaceful bacteria engage in a one-sided relationship with pathogen Porphyromonas gingivalis, helping the germ multiply and cause gum disease, according to a new University at Buffalo-led study.

The research sought to understand how P. gingivalis colonizes the mouth. The pathogen is unable to produce its own growth molecules until it achieves a large population in the oral microbiome (the community of microorganisms that live on and inside the body).

The answer: It borrows growth molecules from V. parvula, a common yet harmless bacteria in the mouth whose growth is not population dependent.

In a healthy mouth, P. gingivalis makes up a miniscule amount of the bacteria in the oral microbiome and cannot replicate. But if dental plaque is allowed to grow unchecked due to poor oral hygiene, V. parvula will multiply and eventually produce enough growth molecules to also spur the reproduction of P. gingivalis.

More than 47% of adults 30 and older have some form of periodontitis (also known as gum disease), according to the Centers for Disease Control and Prevention.

Understanding the relationship between P. gingivalis and V. parvula will help researchers create targeted therapies for periodontitis, says Patricia Diaz, DDS, Ph.D., lead investigator on the study and Professor of Empire Innovation in the UB School of Dental Medicine.

“Having worked with P. gingivalis for nearly two decades, we knew it needed a large population size to grow, but the specific processes that drive this phenomenon were not completely understood,” says Diaz, also director of the UB Microbiome Center.

“Successfully targeting the accessory pathogen V. parvula should prevent P. gingivalis from expanding within the oral microbial community to pathogenic levels.”

The study, which was published on Dec. 28 in the ISME Journal, tested the effects of growth molecules exuded by microorganisms in the mouth on P. gingivalis, including molecules from five species of bacteria that are prevalent in gingivitis, a condition that precedes periodontitis.

Of the bacteria examined, only growth molecules secreted by V. parvula enabled the replication of P. gingivalis, regardless of the strain of either microbe. When V. parvula was removed from the microbiome, growth of P. gingivalis halted. However, the mere presence of any V. parvula was not enough to stimulate P. gingivalis, as the pathogen was only incited by a large population of V. parvula.

Data suggest that the relationship is one-directional as V. parvula received no obvious benefit from sharing its growth molecules, says Diaz.

“P. gingivalis and V. parvula interact at many levels, but the beneficiary is P. gingivalis,” says Diaz, noting that V. parvula also produces heme, which is the preferred iron source for P. gingivalis.

“This relationship that allows growth of P. gingivalis was not only confirmed in a preclinical model of periodontitis, but also, in the presence of V. parvula, P. gingivalis could amplify periodontal bone loss, which is the hallmark of the disease,” says George Hajishengallis, DDS, Ph.D., co-investigator on the study and Thomas W. Evans Centennial Professor in the University of Pennsylvania School of Dental Medicine.

“It is not clear whether the growth-promoting cues produced by P. gingivalis and V. parvula are chemically identical,” says Diaz. “Far more work is needed to uncover the identity of these molecules.”


Non‐communicable diseases (NCDs) are rising in prevalence globally in line with an increasingly ageing population, refined diets and sedentary lifestyles and account for 41 million deaths each year, or 71% of all global deaths (G. B. D. Risk Factors Collaborators, 2016).

Approximately 80% of people over 65‐years of age in the United States are affected by one or more NCDs and 77% exhibit at least two NCDs, creating a significant burden of disease to individuals and to the healthcare economy (Centres for Disease Control & Prevention, 2011).

The comorbid presence of two or more NCDs presents a major challenge to the economy, equating to two‐thirds of all health costs in the United States (Centres for Disease Control & Prevention, 2013); however, <1% USA health expenditure is focussed on prevention to improve overall health (U.S. Senate Committee on Health, 2011).

The greatest global NCD burden arises due to cardiovascular disease (CVD), responsible for 17.9 million deaths (a third of total mortality), and 45% of NCD‐induced mortality (Roth et al., 2017).

In Europe, CVD is responsible for 3.9 million deaths (45% of deaths), and whilst CVD mortality rates are reducing, the absolute numbers have increased in the last 25 years, due to an increasingly ageing population (Wilkins et al., 2017). Ischaemic heart disease, stroke, hypertension (leading to heart failure), rheumatic heart disease, cardiomyopathy and atrial fibrillation cause over 95% of CVD‐related deaths (Roth et al., 2015).

In this consensus report, the term CVD is used as a general term for atherosclerotic diseases, principally coronary heart disease, cerebrovascular disease and peripheral vascular disease. A number of chronic infectious, inflammatory and immune diseases are associated with significantly higher risks of adverse cardiovascular events, including rheumatoid arthritis, psoriasis, systemic lupus erythematosus and periodontitis (Roth et al., 2015), consistent with the thesis that chronic elevations in the systemic inflammatory burden are causally related to CVD development and its sequelae.

Whilst there is evidence for over 50 gene polymorphisms playing a role in the modulation of atherogenesis (Holdt & Teupser, 2015), effect sizes are small and the major traditional risk factors for CVD remain the lifestyle factors, principally tobacco smoking, dyslipidaemia, hypertension and altered glucose metabolism.

The latter correlate strongly with diets high in saturated fats, salt and refined sugars and contribute to obesity and type 2 diabetes mellitus, major attributable risk factors for myocardial infarction (Joseph et al., 2017). The same risk factors account for over 90% of the stroke burden (O’Donnell et al., 2016), yet all are modifiable through improved lifestyles including reducing salt, saturated fat and refined carbohydrate intake, exercising, increasing intake of antioxidant micronutrients and regular moderate alcohol consumption (Joseph et al., 2017).

Periodontitis is also a NCD with a high prevalence of 45%–50% overall, with the most severe form affecting 11.2% of the world’s population, being the sixth most common human disease (Kassebaum et al., 2014). The Global Burden of Diseases, Injuries, and Risk Factors Study (2017) of years lost to disability (YLD) reported that from 1990 to 2017 oral diseases (mainly periodontitis and caries) contributed the most YLD in age‐standardized prevalence rates from 354 diseases and injuries across 195 countries (G. B. D. Disease Injury & Incidence & Prevalence Collaborators, 2018).

There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs including diabetes (Chapple, Genco, & Working group 2013 of the joint EFP/AAP Workshop, 2013), cardiovascular disease (Tonetti et al., 2013), chronic obstructive pulmonary disease (Linden, Lyons, & Scannapieco, 2013) and chronic kidney disease (CKD) (Sharma, Dietrich, Ferro, Cockwell, & Chapple, 2016).

Indeed, severe periodontitis is independently and significantly associated with all‐cause and cardiovascular mortality in several different populations (Linden et al., 2012; Sharma et al., 2016). Proposed mechanisms include bacteraemia and the associated systemic inflammatory sequelae, including elevations in C‐reactive protein and oxidative stress (Schenkein & Loos, 2013).

In populations with multimorbidity, for example chronic kidney disease with comorbid diabetes and periodontitis, periodontitis is associated with significantly reduced survival from all‐cause and cardiovascular mortality (Sharma et al., 2016). It appears therefore that periodontitis may be a modifiable non‐traditional risk factor for CVD.

In 2012, a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. The consensus report was based upon four technical papers that systematically reviewed the evidence for epidemiological associations between periodontitis and incident CVD (Dietrich, Sharma, Walter, Weston, & Beck, 2013), mechanisms of biological plausibility relating to periodontal bacteria and systemic inflammation (Reyes, Herrera, Kozarov, Roldan, & Progulske‐Fox, 2013; Schenkein & Loos, 2013) and periodontal intervention studies (D’Aiuto, Orlandi, & Gunsolley, 2013).

The workshop concluded that there was consistent and strong epidemiological evidence that periodontitis imparts increased risk for future atherosclerotic cardiovascular disease. It also concluded that the impact of periodontitis on CVD was biologically plausible, via translocated circulating oral microbiota, which may directly or indirectly induce systemic inflammation that impacts upon the development of atherothrombogenesis, and whilst in vitro, pre‐clinical and clinical studies supported the interaction and associated biological mechanisms, intervention trials were not sufficiently adequate to draw further conclusions at that time.

The present workshop was jointly organized by the EFP and the World Heart Federation (WHF) to include global experts in both periodontal and cardiovascular disciplines and was held in Madrid on 18th and 19th February 2019. Four technical reviews updating the evidence base from the 2012 workshop were prepared and supplemented by additional studies discussed at the workshop.

The reviews focussed on epidemiological associations (Herrera, Molina, Buhlin, & Klinge, 2019), mechanistic links (Schenkein, Papapanou, Genco, & Sanz, 2019), results from intervention studies (Orlandi, Graziani, & D’Aiuto, 2019) and the potential risk and complications of periodontal therapy in patients undertaking antithrombotic (antiplatelet and anticoagulant) therapy.

Whilst this consensus report focuses predominantly on relevant evidence published since the 2012 workshop, there are biological areas that have subsequently come to prominence, where the underpinning body of evidence was not covered in the 2013 consensus report, and hence, certain pre‐2012 manuscripts are referenced to ensure the context of these recent studies is clear.

Furthermore, section 4.3 “What is the effect of statin intake on clinical periodontal outcomes?” and section 5 “Cardiovascular risks and complications of periodontal therapeutic interventions” were not dealt in the previous workshop, and hence, a full appraisal of the scientific evidence was carried out in this consensus meeting.

Finally, following the review of the presented evidence, recommendations for both medical and dental teams, as well as patients and the public, were elaborated.

reference link: https://onlinelibrary.wiley.com/doi/full/10.1111/jcpe.13189


More information: Anilei Hoare et al. A cross-species interaction with a symbiotic commensal enables cell-density-dependent growth and in vivo virulence of an oral pathogen, The ISME Journal (2020). DOI: 10.1038/s41396-020-00865-y

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