NLRP3 inflammasome activity and periodontal disease pathogenesis-A bidirectional relationship.

OBJECTIVE: Periodontitis is an inflammatory oral disease that occurs as a result of the damaging effects of the immune response against the subgingival microflora. Among the mechanisms involved, the nucleotide-binding oligomerization domain, leucine-rich repeat-containing proteins family member NLRP3 (NLR family pyrin domain-containing 3), proposed as the key regulator of macrophage-induced inflammation, is strongly associated with periodontal disease due to the bacterial activators. This paper aimed to present key general concepts of NLRP3 inflammasome activation and regulation in periodontal disease. METHOD: A narrative review was conducted in order to depict the current knowledge on the relationship between NLRP3 inflammasome activity and periodontal disease. In vitro and in situ studies were retrieved and commented based on their relevance in the field. RESULTS: The NLRP3 inflammasome activity stimulated by periodontal microbiota drive periodontal disease pathogenesis and progression. This occurs through the release of proinflammatory cytokines IL-1ß, IL-18, and DAMPs (damage-associated molecular pattern molecules) following inflammasome activation. Moreover, the tissue expression of NLRP3 is dysregulated by oral microbiota, further exacerbating periodontal inflammation. CONCLUSION: The review provides new insights into the relationship between the NLRP3 inflammasome activity and periodontal disease pathogenesis, highlighting the roles and regulatory mechanism of inflammatory molecules involved in the disease process.

Mirdza E. Neiders: A pioneer in oral pathology, oral health science research, and education.

Over her near 60-year career, Mirdza E. (Mitzi) Neiders has served as a teacher, dentist, researcher, mentor, role-model, friend, and critic for thousands of faculty, students, and patients of the University at Buffalo School of Dental Medicine. One of the first women to serve on the dental school faculty, this article describes her journey and the great impact that she has made on dentistry and her community on the occasion of her retirement.

Modeling longitudinal oral health status and pneumonia risk: secondary data analyses of an integrated dental-medical cohort.

BACKGROUND: Mounting evidence indicates potential associations between poor oral health status (OHS) and increased pneumonia risk. Relative pneumonia risk was assessed in the context of longitudinally documented OHS. METHODS: Electronic medical/dental patient data captured from 2007 through 2019 were retrieved from the integrated health records of Marshfield Clinic Health Systems. Participant eligibility initiated with an assessment of OHS, stratified into the best, moderate, or worst OHS groups, with the additional criterion of 'no pneumonia diagnosis in the past 90 days'. Pneumonia incidence was longitudinally monitored for up to 1 year from each qualifying dental visit. Models were assessed, with and without adjustment for prior pneumonia incidence, adjusted for smoking and subjected to confounding mitigation attributable to known pneumonia risk factors by applying propensity score analysis. Time-to-event analysis and proportional hazard modeling were applied to investigate relative pneumonia risk over time among the OHS groups. RESULTS: Modeling identified associations between any incident pneumonia subtype and 'number of missing teeth' (p < 0.001) and 'clinically assessed periodontal status' (p < 0.01), which remained significant following adjustment for prior pneumonia incidence and smoking. The hazard ratio (HR) for 'any incident pneumonia' in the best OHS group for 'number of missing teeth' was 0.65, 95% confidence interval (CI) [0.54 - 0.79] (unadjusted) and 0.744, 95% CI [0.61 - 0.91] (adjusted). The HR for 'any incident pneumonia' in the best 'clinically assessed periodontal status' group was 0.72, 95% CI [0.58 - 0.90] (unadjusted) and 0.78, 95% CI [0.62 - 0.97] (adjusted). CONCLUSION/CLINICAL RELEVANCE: Poor OHS increased pneumonia risk. Proactive attention of medical providers to patient OHS and health literacy surrounding oral-systemic disease association is vital, especially in high-risk populations.

Oral health status and the etiology and prevention of nonventilator hospital-associated pneumonia.

Nonventilator hospital-associated pneumonia has recently emerged as an important preventable hospital-associated infection, and is a leading cause of healthcare-associated infection. Substantial accumulated evidence links poor oral health with an increased risk of pneumonia, which can be caused by bacterial, viral, or fungal pathogens, each with their own distinct mechanisms of transmission and host susceptibility. These infections are frequently polymicrobial, and often include microbes from biofilms in the oral cavity. Evidence documenting the importance of oral care to prevent nonventilator hospital-associated pneumonia is continuing to emerge. Reduction of oral biofilm in these populations will reduce the numbers of potential respiratory pathogens in the oral secretions that can be aspirated, which in turn can reduce the risk for pneumonia. This review summarizes up-to-date information on the role of oral care in the prevention of nonventilator hospital-associated pneumonia.

Periodontitis is a factor associated with dyslipidemia.

OBJECTIVE: To investigate the association between the severity of periodontitis (exposure) and dyslipidemia (outcome). METHODS: This was a cross-sectional study of users of public health services. Periodontitis was defined using the Center for Disease Prevention and Control and the American Academy of Periodontology criteria. Lipid evaluation used data on systemic biomarkers. Dyslipidemia diagnosis was based on the Guidelines of total cardiovascular risk of the World Health Organization. Weight, height, waist circumference, and blood pressure were measured, and socioeconomic-demographic, lifestyle behavior factors, general and oral health conditions of the participants were collected. Hierarchical and logistic regression analyzes were used to determine the association between the exposures and the outcome. Odds Ratios, unadjusted and adjusted, and 95% confidence intervals were estimated. RESULTS: Of 1,011 individuals examined, 75.17% had dyslipidemia, and 84.17% had periodontitis, 0.2% with mild, 48.56% moderate, and 35.41% severe disease. The association between periodontitis and dyslipidemia was maintained through hierarchical analysis and in the multiple regression modeling, showing that the occurrences of dyslipidemia in the group with periodontitis, and its moderate and severe levels, were, respectively, 14%, 30%, and 16% higher compared with those without periodontitis. CONCLUSIONS: The results showed a positive association between moderate and severe periodontitis and dyslipidemia.

Moderate and severe periodontitis are positively associated with metabolic syndrome.

OBJECTIVE: This study investigated the association between periodontitis severity (exposure) and metabolic syndrome (MetS - outcome), using two criteria for diagnosis of the outcome, since this relationship remains unexplored. MATERIALS AND METHODS: A case-control study was conducted with 870 individuals: 408 with first MetS diagnosis (cases) and 462 without MetS (controls). Participants' general information was obtained using a questionnaire and laboratory data was collected from medical records. Periodontitis severity criteria followed the Center for Disease Control and Prevention: none, mild, moderate, and severe. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by logistic regression analysis. RESULTS: Findings showed a positive association between moderate and severe periodontitis and MetS: ORadjusted = 1.64 (95% CI: 1.01 to 2.68) and ORadjusted = 1.94 (95% CI: 1.19 to 3.16), respectively, after adjustment for age, sex, schooling level, smoking habit, and cardiovascular disease. The adjusted measurements showed that among individuals with moderate or severe periodontitis, the probability of having MetS was around two times greater than among those without periodontitis, and that the chance was greater among participants with severe periodontitis than those with moderate periodontitis. CONCLUSION: An association between the severity of periodontal status and MetS was found, suggesting a possible relationship between the two diseases. CLINICAL RELEVANCE: MetS influences the etiology of cardiovascular diseases, one of the leading causes of mortality worldwide. The findings suggest that the greater the severity of periodontitis, the greater is the association magnitude with MetS. The health professional needs to recognize that the importance of periodontal disease may play in MetS.

Associations between dental caries and systemic diseases: a scoping review.

BACKGROUND: The objective of this study was to evaluate and present evidence from animal and human clinical studies on associations between dental caries and systemic diseases, and to suggest potential mechanisms that might explain such associations. METHODS: An electronic search was conducted of PubMed, Embase and Cochrane Central Register of Controlled Trials for articles published from 2010 to 2020 in the English language. From the initial search, 404 full-text studies were assessed for eligibility. After excluding studies for technical and study limitations, a total of 67 studies were included in the summary tables and additional studies were included in the review to support evidence. RESULTS: Few systemic disease and conditions were found to be clinically meaningfully associated with caries experience. Best evidence from human and animal studies described association between metabolic diseases and dental caries. Several interesting animal studies were noted that could generate clinical hypotheses and further investigations in rodent models for cardiovascular injury and hyperglycemia. Inadequate data was found to suggest any modifications to current clinical practice or prevention guidelines. CONCLUSIONS: Limited clinical evidence was found connecting several systemic diseases and dental caries. Inadequate data was found to suggest any modifications to current clinical practice or prevention guidelines. CLINICAL SIGNIFICANCE: Understanding of associations between dental caries and systemic diseases play a crucial role in the treatment planning and education of the dental patient.

The prevention of periodontal disease-An overview.

It is widely accepted that common diseases of the oral cavity, such as gingivitis and periodontitis, are preventable. Based on a large body of scientific evidence, a number of preventive strategies are known to prevent these diseases, but only if routinely implemented. Unfortunately, while most preventive strategies are theoretically simple to understand, they are often difficult to employ in practice at individual and public health levels. This volume of Periodontology 2000 provides the most current information on the state of the science and the evidence base supporting a preventive perspective for the management of periodontal disease, including evidence for proven interventions as well as cutting-edge ideas for potential future interventions. In addition to well-established and scientifically proven approaches (tooth and implant cleansing, topical chemotherapeutics, reduction in risk factors such as tobacco smoking), a number of new ideas are now under investigation, including antioxidant agents, probiotics, vaccines, and slow-release alternative chemotherapeutics. Furthermore, there are new ideas to alter patient behaviors with the aim to improve adherence to preventive strategies. Finally, examples from implementation science and public health are provided that suggest novel approaches to bring new ideas into clinical practice.

Oral-lung microbiome interactions in lung diseases.

The proximity and continuity of the oral cavity and the lower respiratory tract allows the oropharyngeal microbiome to be a major determinant of the lung microbiome. In addition, host-pathogen interactions related to the oropharyngeal microbiome or its metabolites could propagate systemic inflammation or modulate host defense mechanisms that could affect other organs, including the lung. There is increasing appreciation of the pathophysiologic significance of the lung microbiome, not only in the classical infection-related diseases, pneumonia, bronchiectasis, and cystic fibrosis, but also in chronic noninfectious lung diseases, such as chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. In this review, we will explore the relationship of the oral microbiome with lung diseases, such as pneumonia, chronic obstructive pulmonary disease, asthma, and cystic fibrosis.

Obesity and periodontitis are not associated in pregnant women.

OBJECTIVE: The objective of this study was to investigate an association between obesity (exposure) and periodontitis (outcome) in pregnant women. BACKGROUND: This association was investigated and only five studies were identified as showing a positive association. However, some of these studies had limitations such as reduced sample sizes, inadequate exposure criteria and outcome measures, which question the internal validity of these investigations. METHODS: A cross-sectional study was carried out with a sample of 644 pregnant women of the public health service of the municipality of Santo Antônio de Jesus, Bahia, Brazil. Data were obtained by collecting of socioeconomic-demographic information, health behavior, health conditions, and reproductive history through an interview. Obesity was evaluated using body mass index adjusted for gestational age and expected weight gain. The diagnosis of periodontitis followed two criteria: (a) Center for Disease Prevention and Control and American Academy of Periodontology (CDC/AAP); (b) Gomes-Filho et al (2018) using criterion that also evaluated bleeding upon probing; Prevalence ratios and respective 95% confidence intervals were obtained by Poisson regression analysis. RESULTS: In accordance with the outcome diagnostic criterion, the frequency of periodontitis was 17.24% (Gomes-Filho et al) and 66.92% (CDC/AAP). The participants were classified as low weight (19.72%), adequate weight (42.39%), overweight (24.84%), and obesity (13.04%), based on the exposure diagnostic criterion. The low weight and overweight groups were excluded from the data analysis, giving a final sample of 357 pregnant women. The association between obesity in pregnant women and periodontitis was not statistically significant, after adjusting for confounders such as age, schooling level, alcoholic beverage consumption, alimentary and nutritional orientation, urinary infection, and dental flossing. CONCLUSIONS: The findings showed a high frequency of periodontitis, obesity, and overweight in the studied population but no association between obesity and periodontitis in pregnant women was found.

Periodontitis and respiratory diseases: A systematic review with meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the recent scientific literature addressing the association between periodontitis and asthma, chronic obstructive pulmonary disease (COPD), and pneumonia. MATERIALS AND METHODS: The search for studies was carried out using MEDLINE/PubMed, EMBASE, Lilacs, Web of Science, Scopus, and SciELO databases, including the gray literature (ProQuest). Reference lists of selected articles were also searched. Studies having varying epidemiological designs assessing the association between periodontitis and respiratory diseases in human subjects were eligible for inclusion. Three independent reviewers performed the selection of articles and data extraction. Fixed and random effects meta-analysis were performed for the calculation of the association measurements (Odds Ratio-OR) and 95% confidence intervals (95% CI). RESULTS: A total of 3,234 records were identified in the database search, with only 13 studies meeting the eligibility criteria and 10 studies contributed data for meta-analysis. Using a random effects models periodontitis was associated with asthma: ORadjusted: 3.54 (95% CI: 2.47-5.07), I2  = 0%; with COPD: OR adjusted: 1.78 (95% CI: 1.04-3.05), I2  = 37.9%; and with pneumonia: OR adjusted: 3.21 (95% CI: 1.997-5.17), I2  = 0%. CONCLUSIONS: The main findings of this systematic review validated an association between periodontitis and asthma, COPD and pneumonia.

Is there association between stress and periodontitis?

OBJECTIVE: This study estimated the association between stress and periodontitis. MATERIALS AND METHODS: A cross-sectional study was conducted with a sample of 621 individuals. Information about individuals was obtained through a questionnaire. Stress was evaluated using the Perceived Stress Scale. The diagnosis of periodontitis was based on a complete periodontal examination including clinical attachment level, probing depth, and bleeding on probing. Prevalence ratios (PR), crude and adjusted, and their respective 95% confidence intervals (95%CI) were estimated by Poisson regression analysis. RESULTS: In the final sample, 48.47% (301) of the individuals were classified as having stress, of which, 23.92% (72) had the diagnosis of periodontitis. Association measurements between stress and probing depth ≥ 4 mm (PRadjusted = 1.28, 95%CI [1.04 to 1.58]), stress and clinical attachment level ≥ 5 mm (PRadjusted = 1.15, 95%CI [1.01 to 1.31]), and stress and periodontitis (PRadjusted = 1.36, 95%CI [1.01 to 1.83]) showed that the frequency of these outcomes among those exposed to stress was 15-36% higher than those without the condition of stress, after adjustment for age, sex, schooling level, current smoking habit, pulmonary disease, and body mass index. CONCLUSIONS: The findings showed positive association between exposure to stress and the presence of periodontitis, reaffirming the need to prevent and control stress. CLINICAL RELEVANCE: Although there are limitations in this study, the results showed that an association exists between stress and periodontitis, signaling the necessity of a multidisciplinary attention when considering the psychological status in the management of oral and general health conditions of the individual.

Veillonella infantium sp. nov., an anaerobic, Gram-stain-negative coccus isolated from tongue biofilm of a Thai child.

A strain of a novel anaerobic, Gram-stain-negative coccus was isolated from the tongue biofilm of a Thai child. This strain was shown, at the phenotypic level and based on 16S rRNA gene sequencing, to be a member of the genus Veillonella. Comparative analysis of the 16S rRNA, dnaK and rpoB gene sequences indicated that phylogenetically the strain comprised a distinct novel branch within the genus Veillonella. The novel strain showed 99.8, 95.1 and 95.9 % similarity to partial 16S rRNA, dnaK and rpoB gene sequences, respectively, to the type strains of the two most closely related species, Veillonelladispar ATCC 17748T and Veillonellatobetsuensis ATCC BAA-2400T. The novel strain could be discriminated from previously reported species of the genus Veillonella based on partial dnaK and rpoB gene sequencing and average nucleotide identity values. The major acid end-product produced by this strain was acetic acid under anaerobic conditions in trypticase-yeast extract-haemin with 1 % (w/v) glucose or fructose medium. Lactate was fermented to acetic acid and propionic acid. Based on these observations, this strain represents a novel species, for which the name Veillonella infantium sp. nov. is proposed. The type strain is T11011-4T (=JCM 31738T=TSD-88T).

Role of periodontal therapy in management of common complex systemic diseases and conditions: An update.

The goal of this review is to summarize the results of randomized trials reported since 2010 that assessed the effect of periodontal interventions on at least one systemic outcome in human subjects of any age, gender or ethnicity. Oral outcome measures included gingivitis, pocket depth, clinical attachment loss and/or radiographic bone loss and oral hygiene indices. Studies were excluded if the trial was not completed or if treatment was not randomized. The results suggest that nonsurgical periodontal intervention provided to pregnant women is safe and improves periodontal status without preventing adverse pregnancy outcomes. Nonsurgical periodontal intervention was also found to provide modest improvement in glycemic control in individuals with type 2 diabetes mellitus and periodontitis. Also, improving oral care through mechanical or chemical control of dental-plaque biofilm formation can contribute to the prevention of respiratory infections in differing clinical settings, including hospitals and nursing homes, and in patients with chronic obstructive pulmonary disease. No clinical trials were reported that tested the effect of periodontal interventions on medical outcomes of atherosclerosis, cardiovascular diseases, stroke, rheumatoid arthritis, Alzheimer's disease, chronic kidney disease or malignant neoplasia.

Association between periodontitis and severe asthma in adults: A case-control study.

OBJECTIVE: To evaluate the association between periodontitis and severe asthma, with participants in treatment for severe asthma, controlled by therapy. METHODS: A case-control investigation was performed to compare 130 adults with severe asthma with 130 without asthma. Individuals with periodontitis were those with ≥4 teeth with ≥1 site with probing depth ≥4 mm, clinical attachment level ≥3 mm, and bleeding upon probing at the same site. Severe asthma diagnosis was based on Global Initiative for Asthma criteria. RESULTS: Association between exposure to periodontitis and severe asthma was found: ORcrude  = 2.98 (95% CI: 1.74-5.11). When confounders were considered, the association between exposure to periodontitis and severe asthma was maintained: ORadjusted  = 3.01-3.25. Individuals with periodontitis had about a threefold increased risk of severe asthma than those without periodontitis. Frequency of periodontitis in participants with severe asthma was greater than that of those without asthma (46.6% vs 22.3%, p ≤ .05). CONCLUSIONS: Association between periodontitis and severe asthma was observed. Further investigation is required to determine the direction of this relationship. It may be causal, but it may also be a consequence of the immunopathological process that characterizes asthma, or else, consequence of the medication used for treatment.

Estimated prevalence of halitosis: a systematic review and meta-regression analysis.

OBJECTIVE: This study aims to conduct a systematic review to determine the prevalence of halitosis in adolescents and adults. METHODS: Electronic searches were performed using four different databases without restrictions: PubMed, Scopus, Web of Science, and SciELO. Population-based observational studies that provided data about the prevalence of halitosis in adolescents and adults were included. Additionally, meta-analyses, meta-regression, and sensitivity analyses were conducted to synthesize the evidence. RESULTS: A total of 584 articles were initially found and considered for title and abstract evaluation. Thirteen articles met inclusion criteria. The combined prevalence of halitosis was found to be 31.8% (95% CI 24.6-39.0%). Methodological aspects such as the year of publication and the socioeconomic status of the country where the study was conducted seemed to influence the prevalence of halitosis. CONCLUSIONS: Our results demonstrated that the estimated prevalence of halitosis was 31.8%, with high heterogeneity between studies. The results suggest a worldwide trend towards a rise in halitosis prevalence. CLINICAL RELEVANCE: Given the high prevalence of halitosis and its complex etiology, dental professionals should be aware of their roles in halitosis prevention and treatment.

Identification of an early stage biofilm inhibitor from Veillonella tobetsuensis.

Oral biofilm, the cause of dental caries and periodontal diseases, consists of multiple bacterial species. Streptococcus spp. and Veillonella spp. have been reported as to be initial and early colonizers of oral biofilms. Our previous studies showed that Veillonella tobetsuensis may play an important role on the development of S. gordonii biofilms without coaggregation involving extracellular biomolecules. In this study, the effect of a cyclic dipeptide autoinducer from culture supernatants from V. tobetsuensis at late-exponential growth phase on S. gordonii biofilm was examined. The cyclic dipeptide, identified as cyclo (-L-Leu-L-Pro) by gas chromatography/mass spectrometry, inhibited the development of S. gordonii biofilm. Furthermore, cyclo (-L-Leu-L-Pro) appeared not to cause bactericidal effects on planktonic cells of S. gordonii. This is the first report that oral Veillonella produces cyclo (-L-Leu-L-Pro) in their culture supernatants. Moreover, the results of this study suggest that cyclo (-L-Leu-L-Pro) may have an application to inhibit early stage development of oral biofilms.

Establishment of a species-specific primer pair for detecting Veillonella infantium based on the 70 kDa heat shock protein gene dnaK.

Recently, Veillonella infantium was isolated from tongue biofilm of a Thai child and established as a novel Veillonella species. In this study, a species-specific primer was designed to identify V. infantium on the basis of the sequence of the 70 kDa heat shock protein (dnaK) gene of Veillonella infantium JCM 31738T (= TSD-88T). The primer pair generated a specific PCR (Polymerase Chain Reaction) product specific for V. infantium, but not for other oral Veillonella species. This specific primer pair could detect dnaK even from 1 pg of genomic DNA extracted from the V. infantium type strain. To validate the primer pair, a number of strains of Veillonella species were isolated from tongue biofilm of 3 Japanese children, DNA was isolated from each strain, and PCR was performed using species-specific primers. All oral Veillonella species except V. infantium were identified by one-step PCR method reported previously. Four kinds of Veillonella species were detected in these subjects. V. rogosae was detected in all subjects and the most predominant species with an average prevalence of 82%. However, V. infantium was detected in 2 of 3 subjects and it was the second most predominant species of oral Veillonella detected in these subjects with an average prevalence of 9.4%. V. infantium appears to coexist with other oral Veillonella species in tongue biofilm. This species-specific primer pair established in this study could be useful to detect V. infantium and support the study of Veillonella for oral health in the future.

Comparative genomics and evolution of the amylase-binding proteins of oral streptococci.

BACKGROUND: Successful commensal bacteria have evolved to maintain colonization in challenging environments. The oral viridans streptococci are pioneer colonizers of dental plaque biofilm. Some of these bacteria have adapted to life in the oral cavity by binding salivary α-amylase, which hydrolyzes dietary starch, thus providing a source of nutrition. Oral streptococcal species bind α-amylase by expressing a variety of amylase-binding proteins (ABPs). Here we determine the genotypic basis of amylase binding where proteins of diverse size and function share a common phenotype. RESULTS: ABPs were detected in culture supernatants of 27 of 59 strains representing 13 oral Streptococcus species screened using the amylase-ligand binding assay. N-terminal sequences from ABPs of diverse size were obtained from 18 strains representing six oral streptococcal species. Genome sequencing and BLAST searches using N-terminal sequences, protein size, and key words identified the gene associated with each ABP. Among the sequenced ABPs, 14 matched amylase-binding protein A (AbpA), 6 matched amylase-binding protein B (AbpB), and 11 unique ABPs were identified as peptidoglycan-binding, glutamine ABC-type transporter, hypothetical, or choline-binding proteins. Alignment and phylogenetic analyses performed to ascertain evolutionary relationships revealed that ABPs cluster into at least six distinct, unrelated families (AbpA, AbpB, and four novel ABPs) with no phylogenetic evidence that one group evolved from another, and no single ancestral gene found within each group. AbpA-like sequences can be divided into five subgroups based on the N-terminal sequences. Comparative genomics focusing on the abpA gene locus provides evidence of horizontal gene transfer. CONCLUSION: The acquisition of an ABP by oral streptococci provides an interesting example of adaptive evolution.