Periodontal Disease

Longitudinal monitoring of patients suggests a causal link between chronic periodontitis and the development of Alzheimer’s disease (AD). However, the explanation of how periodontitis can lead to dementia remains unclear. A working hypothesis links extrinsic inflammation as a secondary cause of AD. This hypothesis suggests a compromised oral hygiene leads to a dysbiotic oral microbiome whereby Porphyromonas gingivalis, a keystone periodontal pathogen, with its companion species, orchestrates immune subversion in the host. Brushing and chewing on teeth supported by already injured soft tissues leads to bacteremias. As a result, a persistent systemic inflammatory response develops to periodontal pathogens. The pathogens, and the host’s inflammatory response, subsequently lead to the initiation and progression of multiple metabolic and inflammatory co-morbidities, including AD. Insufficient levels of essential micronutrients can lead to microbial dysbiosis through the growth of periodontal pathogens such as demonstrated for P. gingivalis under low hemin bioavailability. An individual’s diet also defines the consortium of microbial communities that take up residency in the oral and gastrointestinal (GI) tract microbiomes. Their imbalance can lead to behavioral changes. For example, probiotics enriched in Lactobacillus genus of bacteria, when ingested, exert some anti-inflammatory influence through common host/bacterial neurochemicals, both locally, and through sensory signaling back to the brain. Early life dietary behaviors may cause an imbalance in the host/microbial endocrinology through a dietary intake incompatible with a healthy GI tract microbiome later in life. This imbalance in host/microbial endocrinology may have a lasting impact on mental health. This observation opens up an opportunity to explore the mechanisms, which may underlie the previously detected relationship between diet, oral/GI microbial communities, to anxiety, cognition and sleep patterns. This review suggests healthy diet based interventions that together with improved life style/behavioral changes may reduce and/or delay the incidence of AD.

Periodontal diseases, such as chronic periodontitis, share common inflammatory risk factors with other systemic and chronic inflammatory disorders. Mucosal tissues, such as oral epithelia, are exposed to environmental stressors, such as tobacco and oral bacteria, that might be involved in promoting a systemic inflammatory state. Conversely, chronic disorders can also affect oral health. This review will summarize recent evidence for the interrelationship between chronic periodontitis and other prevalent chronic diseases such as cardiovascular diseases, diabetes, cancer and chronic respiratory diseases. The association with pregnancy is also included due to possible obstetric complications. We will focus on inflammatory cytokines such as TNF-alpha, IL-1, and IL-6, because they have been shown to be increased in patients with chronic periodontitis, in patients with chronic systemic diseases, and in patients with both chronic periodontitis and other chronic diseases. Therefore, an imbalance towards a proinflammatory immune response could underline a bidirectional link between chronic periodontitis and other chronic diseases. Finally, we highlight that a close coordination between dental and other health professionals could promote oral health and prevent or ameliorate other chronic diseases.

INTRODUCTION:

Numerous studies have demonstrated an association between oral health status and systemic diseases. However, reports examining apical periodontitis (AP) and cardiovascular disease (CVD) are few. This study investigates whether an association exists between AP and CVD.

METHODS:

The present study was a pair-matched, cross-sectional design that used medical and dental chart review. The AP group (n = 182) was defined as subjects with radiographic AP, and the non-AP group (n = 182) was defined as subjects without any radiographic AP. Samples for both groups were pair-matched by age and gender. Diagnosis for CVD, hypercholesterolemia, hypertension, and diabetes were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification and collected from electronic medical records. Documentation of alcohol use, smoking, race, and body mass index within the electronic medical records was also collected. Presence or absence of AP, missing teeth, teeth with root canal treatment, caries experience, and history of periodontal disease were collected from the electronic dental records. Analysis was performed by using Pearson χ(2), the paired t test, and conditional multivariate logistic regression.

RESULTS:

AP was significantly associated with CVD, hypercholesterolemia, race, missing teeth, caries experience, and number of root canal treatments in our bivariate analysis. Our final adjusted conditional logistic regression model showed statistically significant positive associations between AP and CVD (odds ratio, 5.3; 95% confidence interval, 1.5-18.4).
CONCLUSIONS:

Subjects with AP were more likely to have CVD than subjects without AP by 5.3-fold. However, further research is needed to elucidate temporality and reinforce association between CVD and AP.

The relationship between rheumatoid arthritis and poor oral health has been recognised for many decades. The association between periodontal infection and the risk of developing RA has been the subject of epidemiological, clinical and basic science research in recent times. Converging and reproducible evidence now makes a clear case for the role of specific periodontal infective pathogens in initiating, amplifying and perpetuating rheumatoid arthritis. The unique enzymatic properties of the periodontal pathogen Porphyromonas gingivalis and its contribution to the burden of citrullinated peptides is now well established. The impact of localized infection such as periodontitis in shaping specific anti-citrullinated peptide immune responses highlights a key area for treatment, prevention and risk assessment in rheumatoid arthritis.

"This aim of this document is to provide health professionals, especially cardiologists and periodontists, a better
understanding of the link between atherosclerotic CVD and periodontitis and, on the basis of current information, an
approach to reducing the risk for primary and secondary atherosclerotic CVD events in patients with periodontitis."

OBJECTIVE:

To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.

METHODS:

Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression.

RESULTS:

Presence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection.

CONCLUSION:

Both PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.

“Perhaps the most likely carcinogenic link with oral bacteria is with oral squamous cell carcinoma (OSCC), one of the most common cancers worldwide. OSCC surfaces have been reported to harbor significantly higher levels of Porphyromonas and Fusobacterium compared with contiguous healthy mucosa [3]. Moreover, immunohistochemistry with P. gingivalis antibodies revealed higher levels of detection and intensity of staining in gingival carcinomas compared with healthy gingival tissue, although only a small number of cases were examined [4]. A striking association has also been demonstrated between P. gingivalis infection and pancreatic cancer. In a prospective cohort study of over 400 cases and controls, a >2-fold increase in risk of pancreatic cancer was observed among those with high levels of antibodies to P. gingivalis, after adjusting for known risk factors [5]. Similarly, in the extensive National Health and Nutrition Examination Survey III, orodigestive cancer mortality was found to be related to the levels of P. gingivalis antibodies, independent of periodontal disease [6]. Several recent studies have shown a strong association between F. nucleatum and colorectal cancer (CRC) [7]–[10]. F. nucleatum was found to be one of the more abundant species within and around CRC neoplasms, and levels of F. nucleatum correlated with the presence of lymph node metastases.”