Oral health's inextricable connection to systemic health: Special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions

Abstract

The landscape in dentistry is changing as emerging studies continue to reveal that periodontal health impacts systemic health, and vice versa. Population studies, clinical studies, and in vitro animal studies underscore the critical importance of oral health to systemic health. These inextricable relationships come to the forefront as oral diseases, such as periodontal disease, take root. Special populations bring to bear the multimodal relationships between oral and systemic health. Specifically, periodontal disease has been associated with diabetes, metabolic syndrome, obesity, eating disorders, liver disease, cardiovascular disease, Alzheimer disease, rheumatoid arthritis, adverse pregnancy outcomes, and cancer. Although bidirectional relationships are recognized, the potential for multiple comorbidities, relationships, and connections (multimodal relationships) also exists. Proposed mechanisms that mediate this connection between oral and systemic health include predisposing and precipitating factors, such as genetic factors (gene polymorphisms), environmental factors (stress, habits-such as smoking and high-fat diets/consumption of highly processed foods), medications, microbial dysbiosis and bacteremias/viremias/microbemias, and an altered host immune response. Thus, in a susceptible host, these predisposing and precipitating factors trigger the onset of periodontal disease and systemic disease/conditions. Further, high-throughput sequencing technologies are shedding light on the dark matter that comprises the oral microbiome. This has resulted in better characterization of the oral microbial dysbiosis, including putative bacterial periodontopathogens and shifts in oral virome composition during disease. Multiple laboratory and clinical studies have illustrated that both eukaryotic and prokaryotic viruses within subgingival plaque and periodontal tissues affect periodontal inflammation, putative periodontopathogens, and the host immune response. Although the association between herpesviruses and periodontitis and the degree to which these viruses directly aggravate periodontal tissue damage remain unclear, the benefits to periodontal health found from prolonged administration of antivirals in immunocompromised or immunodeficient individuals demonstrates that specific populations are possibly more susceptible to viral periodontopathogens. Thus, it may be important to further examine the implications of viral pathogen involvement in periodontitis and perhaps it is time to embrace the viral dark matter within the periodontal environment to fully comprehend the pathogenesis and systemic implications of periodontitis. Emerging data from the coronavirus disease 2019 pandemic further underscores the inextricable connection between oral and systemic health, with high levels of the severe acute respiratory syndrome coronavirus 2 angiotensin-converting enzyme 2 receptor noted on oral tissues (tongue) and an allostatic load or overload paradigm of chronic stress likely contributing to rapid breakdown of oral/dental, periodontal, and peri-implant tissues. These associations exist within a framework of viremias/bacteremias/microbemias, systemic inflammation, and/or disturbances of the immune system in a susceptible host. A thorough review of systemic and oral diseases and conditions and their mechanistic, predisposing, and precipitating factors are paramount to better addressing the oral and systemic health and needs of our patients.

Keywords: microbemias; oral health; periodontal disease; susceptible host; systemic disease; systemic inflammation.

FIGURE 1

Periodontal disease associations with systemic diseases and conditions. Periodontal disease has been associated with diabetes, metabolic syndrome, obesity, eating disorders, liver disease, cardiovascular disease, Alzheimer disease, rheumatoid arthritis, adverse pregnancy outcomes, and cancer. Proposed mechanisms that mediate this connection between oral and systemic health in a susceptible host include predisposing and precipitating factors, such as genetic factors (gene polymorphisms), environmental factors (stress, habits—such as smoking and high‐fat diets/consumption of highly processed foods), medications, microbial dysbiosis and bacteremias/viremias, and an altered host immune response. These associations exist within a framework of bacteremias/viremias/microbemias, systemic inflammation, and/or disturbances of the immune system in a susceptible host. (Figure courtesy of Dr Ryutaro Kuraji, Assistant Professor, Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan; Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan; Visiting Assistant Professor; Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, USA)

FIGURE 2

Allostatic load and implications for oral and periodontal health. Allostatic load or overload describes the “wear and tear” on the body as a result of chronic stress and how this contributes to pathology. There may be a rapid breakdown of oral, dental, periodontal, and peri‐implant tissues as a result of an allostatic load or overload. For example, from chronic stress due to the coronavirus disease 2019 (COVID‐19) pandemic, other environmental stressors, major life events, or trauma. This perceived stress is subject to individual differences and then elicits behavioral and physiologic responses. These responses result in allostasis (homeostasis), adaptation, or an allostatic load. The allostatic load or overload paradigm of chronic stress likely contributes to the rapid breakdown/loss of oral tissues due to several mechanisms (neuroendocrine, altered inflammatory or wound healing processes)