Dietary inflammatory index in relation to salivary cytokine concentrations and periodontitis: A cross-sectional analysis.

AIM: To examine the associations of dietary inflammatory index (DII) with salivary cytokine concentrations and periodontitis after controlling for body mass index (BMI), socio-demographic factors and lifestyle. MATERIALS AND METHODS: Subgroups from two Finnish surveys, DILGOM 2007 and Health 2000, were included (total n = 727). The DII scores were calculated based on a food frequency questionnaire. Periodontal status was assessed with a cumulative risk score in DILGOM 2007 and by pocket depth measurement in Health 2000. From saliva, interleukin (IL)-1ß, IL-1 receptor antagonist, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-α concentrations were measured. RESULTS: The DII scores did not differ between non-periodontitis and periodontitis participants in pairwise comparison. After adjusting for energy intake, periodontal status, BMI, age, education level, smoking habit and physical activity, DII was not associated with salivary cytokine concentrations. After adjusting for salivary cytokine levels and other confounding factors, DII was associated with periodontitis in the Health 2000 subgroup but not in the DILGOM 2007 subgroup. CONCLUSIONS: The current data support the evidence that diet is not associated with salivary cytokine levels but may be associated with periodontitis. The association observed between diet and periodontitis is related to factors other than diet-dependent inflammatory tendency in the oral cavity.

Burden of oral diseases predicts development of excess weight in early adolescence: a 2-year longitudinal study.

Dental caries, gingivitis, and excess weight are highly prevalent, interconnected chronic conditions. The association of oral health with the development of adiposity among children is sparsely addressed. We examined the association of oral health to the development of excess weight and central obesity in early adolescence during a 2-year follow-up period. This prospective study was conducted with 2702 children aged 9-12 years at baseline from the Finnish Health in Teens study. Their weight development was followed up for 2 years. Body mass index with age- and sex-specific cut-offs and the waist-height ratio indicated weight status and central obesity. Oral health data (caries experience and gingivitis/calculus) were collected from outpatient records of public dental services. Having both caries experience and gingivitis/calculus was considered burden of oral diseases. Of the sample, 74% were caries-free but 70% exhibited gingivitis and/or calculus, and 20% had both caries experience and gingivitis/calculus. During the follow-up period, 5.3% (n = 124) and 4.7% (n = 118) of the children became overweight/obese or centrally obese, respectively. Having both caries experience and gingivitis/calculus associated with the development of excess weight in a fully adjusted model (HR 1.75, 95% CI 1.03-2.97) but not of central obesity. Caries experience or gingivitis/calculus alone did not associate with adiposity development. CONCLUSION: Having burden of oral diseases without excess weight at early adolescence could imply future weight gain; thus, normal-weight individuals with both caries experience and gingivitis/calculus could be targeted with preventive measures. Our findings warrant further research to explore whether oral diseases and the development of obesity merely share risk factors or if their relationship is of causal nature. WHAT IS KNOWN: • Association of excess weight with caries experience and gingivitis is known to exist both cross-sectionally and longitudinally in children and adolescents. WHAT IS NEW: • Burden of oral diseases, that is, having both caries experience and gingivitis/calculus, was associated with becoming overweight or obese 2 years later during early adolescence. • Normal-weight individuals with burden of oral diseases at early adolescence could be targeted with preventive measures against excess weight gain.

Localization and expression profiles of gingival monocyte chemoattractant protein-1-induced protein-1 (MCPIP-1) and mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT-1).

OBJECTIVES: The purposes of this study were to localize monocyte chemoattractant protein-1-induced protein-1 (MCPIP-1) and its suppressor mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT-1) in gingival tissues and to profile their protein expression levels in relation to the clinical inflammation, Porphyromonas gingivalis colonization, and interleukin (IL)-8 levels. MATERIALS AND METHODS: Study samples were collected from two independent study populations: (1) Gingival tissues were collected from eight periodontally healthy individuals and eight periodontitis patients to localize MCPIP-1 and MALT-1 immunohistochemically, and (2) forty-one gingival tissue samples with marginal, mild, or moderate to severe inflammation were collected from 20 periodontitis patients to determine MCPIP-1 and MALT-1 levels using immunoblots, P. gingivalis levels with qPCR, P. gingivalis gingipain activities with fluorogenic substrates, and IL-8 levels with multiplex technique. RESULTS: MCPIP-1 was detectable in the epithelium and in connective tissue, being especially prominent around the blood vessel walls in healthy periodontal tissues. MALT-1 was observed at all layers of gingival epithelium and especially around the accumulated inflammatory cells in connective tissue. No difference in gingival tissue MCPIP-1 and MALT-1 levels was observed in relation to the severity of gingival inflammation. MALT-1 levels were elevated (p = 0.023) with the increase in tissue P. gingivalis levels, and there was an association between MALT-1 and IL-8 levels (ß = 0.054, p = 0.001). CONCLUSIONS: Interactions of MALT-1 levels with gingival tissue P. gingivalis counts and IL-8 levels suggest that activation of MALT-1 can take part in P. gingivalis-regulated host immune responses. CLINICAL RELEVANCE: Pharmacological targeting the crosstalk between immune response and MCPIP-1/MALT-1 may have benefits in periodontal treatment.

Salivary IgA and IgG Antibody Responses against Periodontitis-Associated Bacteria in Crohn's Disease.

Elevated serum immunoglobulin (Ig) antibody levels are observed in Crohn's disease patients. The aim of this study was to evaluate the salivary IgA and IgG antibody levels against Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia in Crohn's disease patients. Eighty-eight participants (47 Crohn's disease patients and 41 systemically healthy age- and gender-matched controls) were included in the study. Oral and medical health statuses were recorded and salivary samples were collected. Salivary P. gingivalis, T. forsythia, A. actinomycetemcomitans, and P. intermedia carriage were analyzed with DNA sequencing technique, salivary levels of IgG1, IgG2, IgG3, IgG4, and IgM were measured with the Luminex® xMAP™ technique, and salivary IgA and IgG antibody levels against P. gingivalis, T. forsythia, A. actinomycetemcomitans, and P. intermedia were detected by ELISA. As result, higher salivary IgG2 (p = 0.011) and IgG3 (p = 0.006), P. gingivalis IgA (p < 0.001), A. actinomycetemcomitans IgG (p = 0.001), and P. intermedia IgG (p < 0.001) antibody levels were detected in the Crohn's disease group compared to the controls. Salivary P. gingivalis carriage was lower in the Crohn's disease group in comparison to the controls (p = 0.024). In conclusion, salivary IgA antibody responses against P. gingivalis and IgG antibody responses against P. intermedia have independent associations with Crohn's disease.

Blood and saliva SARS-CoV-2 antibody levels in self-collected dried spot samples.

We examined the usefulness of dried spot blood and saliva samples in SARS-CoV-2 antibody analyses. We analyzed 1231 self-collected dried spot blood and saliva samples from healthcare workers. Participants filled in a questionnaire on their COVID-19 exposures, infections, and vaccinations. Anti-SARS-CoV-2 IgG, IgA, and IgM levels were determined from both samples using the GSP/DELFIA method. The level of exposure was the strongest determinant of all blood antibody classes and saliva IgG, increasing as follows: (1) no exposure (healthy, non-vaccinated), (2) exposed, (3) former COVID-19 infection, (4) one vaccination, (5) two vaccinations, and (6) vaccination and former infection. While the blood IgG assay had a 99.5% sensitivity and 75.3% specificity to distinguish participants with two vaccinations from all other types of exposure, the corresponding percentages for saliva IgG were 85.3% and 65.7%. Both blood and saliva IgG-seropositivity proportions followed similar trends to the exposures reported in the questionnaires. Self-collected dry blood and saliva spot samples combined with the GSP/DELFIA technique comprise a valuable tool to investigate an individual's immune response to SARS-CoV-2 exposure or vaccination. Saliva IgG has high potential to monitor vaccination response wane, since the sample is non-invasive and easy to collect.

Periodontitis and cardiometabolic disorders: The role of lipopolysaccharide and endotoxemia.

Lipopolysaccharide is a virulence factor of gram-negative bacteria with a crucial importance to the bacterial surface integrity. From the host's perspective, lipopolysaccharide plays a role in both local and systemic inflammation, activates both innate and adaptive immunity, and can trigger inflammation either directly (as a microbe-associated molecular pattern) or indirectly (by inducing the generation of nonmicrobial, danger-associated molecular patterns). Translocation of lipopolysaccharide into the circulation causes endotoxemia, which is typically measured as the biological activity of lipopolysaccharide to induce coagulation of an aqueous extract of blood cells of the assay. Apparently healthy subjects have a low circulating lipopolysaccharide activity, since it is neutralized and cleared rapidly. However, chronic endotoxemia is involved in the pathogenesis of many inflammation-driven conditions, especially cardiometabolic disorders. These include atherosclerotic cardiovascular diseases, obesity, liver diseases, diabetes, and metabolic syndrome, where endotoxemia has been recognized as a risk factor. The main source of endotoxemia is thought to be the gut microbiota. However, the oral dysbiosis in periodontitis, which is typically enriched with gram-negative bacterial species, may also contribute to endotoxemia. As endotoxemia is associated with an increased risk of cardiometabolic disorders, lipopolysaccharide could be considered as a molecular link between periodontal microbiota and cardiometabolic diseases.

Salivary IgA antibody to malondialdehyde-acetaldehyde associates with mild periodontal pocket depth.

OBJECTIVE: Oxidized epitopes such as malondialdehyde-acetaldehyde (MAA) play a crucial role in the progression of atherosclerosis through activation of the humoral immune response. The exact mechanism of the association between atherosclerosis and periodontal diseases is not fully understood. The aim of the current study is to evaluate the association of oral humoral immune response to oxidized epitopes with parameters of periodontal disease. MATERIALS AND METHODS: The Parogene cohort consist of patients who have undergone coronary angiography due to cardiac symptoms. In this study, 423 patients were randomly selected for an extensive oral examination. Salivary Immunoglobulin A to oxidized epitopes and bacterial antigens was determined by chemiluminescence immunoassay. RESULTS: In a binary logistic regression model adjusted with periodontal disease confounders, periodontal pocket depth (PPD) 4-5 mm associated with salivary IgA antibodies to MAA-LDL (p = 0.034), heat shock protein 60 of Aggregatibacter actinomycetemcomitans (p = 0.045), Porphyromonas gingivalis (p = 0.045), A. actinomycetemcomitans (p = 0.005), P. intermedia (p = 0.020), and total IgA (p = 0.003). CONCLUSIONS: The current study shows the association of salivary IgA to MAA-LDL with PPD 4-5 mm in a cohort of patients with chronic coronary artery disease. Humoral immune cross-reactivation to oxidized epitopes such MAA-LDL could partly explain the link of periodontitis with systemic diseases.

Systemic burden and cardiovascular risk to Porphyromonas species in apical periodontitis.

OBJECTIVE: Porphyromonas (P.) species (spp.) are a major etiological agent of apical periodontitis (AP), which in turn represents a risk factor for cardiovascular diseases. This study explored the associations between endodontic infection with Porphyromonas species, the systemic bacterial burden, and cardiovascular risk, based on high-sensitivity C-reactive protein (hsCRP), in young adults with AP. MATERIALS AND METHODS: Cross-sectional study. Otherwise, healthy individuals with AP and controls (n = 80, ≤ 40 years) were recruited at the University Dental Clinic. Oral parameters and classic cardiovascular risk factors were registered. Endodontic Porphyromonas endodontalis and Porphyromonas gingivalis were identified using conventional PCR. Serum concentrations of anti-P. endodontalis and anti-P. gingivalis antibodies, and endotoxins were determined through ELISA and Limulus-amebocyte assays. Serum hsCRP was determined for cardiovascular risk stratification. RESULTS: Intracanal detection of P. endodontalis and P. gingivalis in AP were 33.3% and 22.9%, respectively. Serum anti-P. endodontalis and anti-P. gingivalis IgG was higher in AP than controls (p < 0.05 and p = 0.057, respectively). Intracanal P. endodontalis associated with higher endotoxemia (p < 0.05). Among endodontic factors, the presence (OR 4.2-5.5, p < 0.05) and the number of apical lesions (OR 2.3, p < 0.05) associated with moderate-severe cardiovascular risk, whereas anti-P. endodontalis IgG were protective (OR 0.3, p > 0.05). CONCLUSIONS: AP and infection with P. endodontalis positively associated with cardiovascular risk based on hsCRP levels and endotoxemia, respectively, whereas anti-P. endodontalis IgG response seems to be protective against low-grade systemic inflammation. CLINICAL RELEVANCE: Apical periodontitis and endodontic P. endodontalis can influence the systemic burden with impact on the surrogate cardiovascular risk marker hsCRP, providing mechanistic links.

Severity and progression rate of periodontitis are associated with an increased risk of hypertension of patients attending a university clinic.

BACKGROUND: Although periodontitis is associated with increased risk of hypertension, studies based on new periodontal disease classification is limited. We investigated whether periodontitis severity and progression rate are linked with self-reports on doctor-diagnosed hypertension in a large cohort of patients attending the periodontology clinic at the faculty of dentistry. METHODS: Archived patient files, including radiographic image records and results from full-mouth clinical periodontal examination were screened for inclusion. Data on socioeconomic factors, smoking and oral hygiene habits, and medical history were collected with a questionnaire. RESULTS: Diagnosis and background data were available for 7008 patients. The median (IQR) age was 31.0 (21.0) years; 60.1% (n = 4211) were female. Hypertension was diagnosed in 6.2% (n = 435) of patients. Both periodontitis stage and grade differed (p < 0.001) between patients with or without hypertension. Increased periodontal disease severity was associated with a 20% increasing risk for hypertension; the odds ratio (OR) was 2.63 (95% confidence interval [CI] 1.48-4.68, p < 0.001) in stage IV periodontitis. Increasing periodontitis progression rate was associated with a 35% increased risk for hypertension; the OR was 2.22 (95% CI 1.45-3.40, p < 0.001) in grade C periodontitis. CONCLUSION: Severity and progression rate of periodontitis may be independent risk factors for hypertension in this large cohort of patients attending the university periodontal department.

Systemic immune response against the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans is associated with the formation and rupture of intracranial aneurysms.

BACKGROUND AND PURPOSE: Periodontal infections are associated with the formation and rupture of intracranial aneurysms (IAs). This study investigated the role of two key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. METHODS: Immunoglobulin A (IgA) and IgG antibodies against P. gingivalis and A. actinomycetemcomitans were measured with enzyme immune assay from the serum of 227 IA patients, of whom 64 also underwent clinical oral examination. As a control group, 1096 participants in a cross-sectional health survey, Health 2000, underwent serological studies and oral examination. Logistic regression was used for multivariate analysis. Immunohistochemistry was performed to demonstrate bacteria-derived epitopes in the IA wall. RESULTS: Widespread gingivitis and severe periodontitis were more common in IA patients than in controls (2× and 1.5×, respectively). IgA antibodies against P. gingivalis and A. actinomycetemcomitans were 1.5× and 3-3.4× higher, respectively, in both unruptured and ruptured IA patients compared to controls (p ≤ 0.003). IgG antibodies against P. gingivalis were 1.8× lower in unruptured IA patients (p < 0.001). In multivariate analysis, high IgA, but low IgG, antibody levels against P. gingivalis (odds ratio [OR] = 1.4, 95% confidence interval [Cl] = 1.1-1.8 and OR = 1.5, 95% Cl = 1.1-1.9; OR = 0.6, 95% Cl = 0.4-0.7 and OR = 0.5, 95% Cl = 0.4-0.7) and against A. actinomycetemcomitans (OR = 2.3, 95% Cl = 1.7-3.1 and OR = 2.1, 95% Cl = 1.5-2.9; OR = 0.6, 95% Cl = 0.4-0.8 and OR = 0.6, 95% Cl = 0.5-0.9) were associated with the risk of IA formation and rupture. Immunohistochemistry showed P. gingivalis epitopes in the IA wall. CONCLUSIONS: Exposure to the periodontal pathogens P. gingivalis and A. actinomycetemcomitans and dysfunctional acquired immune response against them may increase the risk of IA formation and IA rupture.

Role of oral pathogens in the pathogenesis of intracranial aneurysm: review of existing evidence and potential mechanisms.

Degeneration of intracranial aneurysm wall is under active research and recent studies indicate an increased risk of rupture of intracranial aneurysm among patients with periodontal diseases. In addition, oral bacterial DNA has been identified from wall samples of ruptured and unruptured aneurysms. These novel findings led us to evaluate if oral diseases could predispose to pathological changes seen on intracranial aneurysm walls eventually leading to subarachnoid hemorrhage. The aim of this review is to consider mechanisms on the relationship between periodontitis and aneurysm rupture, focusing on recent evidence.

Association of a Multigenetic Pro-Inflammatory Profile with Ischaemic Stroke.

OBJECTIVE: A multigenetic pro-inflammatory profile may increase stroke risk. We investigated whether a higher number of pro-inflammatory genetic variants are associated with ischaemic stroke risk and whether other risk factors further elevate this risk. METHODS: In a case-control study with 470 ischaemic stroke patients (cases) and 807 population controls, we investigated 23 haplotypes or alleles in 16 inflammatory genes (interleukin [IL]1A, IL1B, IL1 receptor antagonist, IL6, IL6 receptor, IL10, tumour necrosis factor-a; C-C motif chemokine ligand 2, C-C motif chemokine receptor 5, C-reactive protein (CRP), intercellular adhesion molecule 1, transforming growth factor ß1, E-Selectin, selenoprotein S, cluster determinant 14, histone deacetylase 9 [HDAC9]). We constructed an extended gene score (EGS) as the sum of all individual risk alleles and analysed its effect on stroke, just as its association and interaction with cardiovascular risk factors and infectious scores (IgG antibodies against 5 respectively IgA antibodies against 4 microbial antigens). RESULTS: Cases were less likely to carry the minor allele of IL10 rs1800872 and more likely to carry the HDAC9 allele rs11984041 and the pro-inflammatory haplotype of CRP, although the latter was not statistically significant in our study. Overall, cases tended to have more pro-inflammatory alleles and haplotypes than controls (mean ± SD 13.25 ± 2.25 and 13.04 ± 2.41, respectively). However, the EGS only slightly and not significantly increased the risk of stroke (OR 1.04, 95% CI 0.99-1.09). Its effect was neither associated with included risk factors nor with IgA and IgG infectious scores, and we found no significant interaction effects. CONCLUSION: A more pro-inflammatory genetic profile might increase stroke risk to some extent. This potential effect is most likely independent of established cardiovascular risk factors and the infectious burden of an individual.

Gingival tissue human beta-defensin levels in relation to infection and inflammation.

AIM: To profile gingival tissue levels of human beta-defensin (hBD)-2 and hBD-3 in relation to gingival inflammation, Th17-related cytokine concentrations, Porphyromonas gingivalis counts, and gingipain and total protease activities. MATERIALS AND METHODS: Gingival tissue and subgingival plaque samples were collected from 21 periodontitis patients including 48 periodontal pocket sites with marginal, mild, or moderate to severe inflammation. hBD levels were determined by immunodetection, P. gingivalis counts with real-time polymerase chain reaction, protease activities with fluorogenic substrates, and cytokine concentrations with Luminex technique. Data were statistically analysed using Kruskal-Wallis and Mann-Whitney U tests and Spearman correlation coefficients. RESULTS: Subgingival plaque counts of P. gingivalis (p = .001) and gingipain activity (p < .001), as well as interleukin (IL)-1ß (p = .012), IL-10 (p = .024), IL-17A (p = .002), IL-17F (p = .006), and IL-23 (p = .036) concentrations were elevated in severely inflamed sites, whereas no change was observed in hBD-2 and hBD-3 levels. Negative correlations were found between protease activity and hBD-2 (p = .033) and hBD-3(p = .003) levels. CONCLUSIONS: Shift in gingival inflammation from marginal to mild stage is related to elevations in subgingival plaque P. gingivalis counts and gingipain activity, but not to tissue hBD levels. Negative correlations between hBDs and total protease activity suggest the degradation of these antimicrobial peptides in progressed inflammation.

Association between periodontitis and risk of Alzheimer's disease, mild cognitive impairment and subjective cognitive decline: A case-control study.

AIMS: To test the hypothesis that periodontal disease contributes to increased risk of mild cognitive impairment (MCI), subjective cognitive decline (SCD) and Alzheimer's disease (AD). MATERIALS AND METHODS: This case-control study was conducted over a 3-year period in the municipality of Huddinge, Sweden. In total, 154 cases were consecutively enrolled from the Karolinska Memory Clinic at the Karolinska University Hospital and allotted to three diagnostic groups: AD, MCI and SCD, collectively referred to as "cases." Seventy-six cognitively healthy age- and gender-matched controls were randomly sampled through the Swedish population register. All cases and controls underwent clinical and radiographic oral examinations. Statistical analysis was based on logistic regression models adjusted for potential confounders. RESULTS: Poor oral health and marginal alveolar bone loss were more prevalent among cases than among controls. The cases group was associated with generalized marginal alveolar bone loss (odds ratio [OR] = 5.81; 95% confidence interval [CI] = 1.14-29.68), increased number of deep periodontal pockets (OR = 8.43; CI 4.00-17.76) and dental caries (OR = 3.36; CI 1.20-9.43). CONCLUSION: The results suggest that marginal periodontitis is associated with early cognitive impairment and AD. However, the study design does not preclude noncausal explanations.

Molecular forms and fragments of salivary MMP-8 in relation to periodontitis.

AIM: To investigate the molecular forms of salivary matrix metalloproteinase (MMP)-8 in relation to periodontitis. MATERIALS AND METHODS: Molecular forms, degree of activation and fragmentation of neutrophilic and mesenchymal-type MMP-8 isoforms were analysed from salivary samples of 81 subjects with generalized periodontitis, 63 subjects with localized periodontitis and 79 subjects without pocket teeth, by using western-immunoblots with computer quantitation. In addition, human recombinant proMMP-8 was in vitro activated by Treponema denticola chymotrypsin-like protease (Td-CTLP), sodium hypochlorite (NaOCl, 1 mM, oxidant) or amino phenyl mercuric acetate (APMA, 1 mM). RESULTS: In saliva of periodontitis-affected individuals, MMP-8 is found in multiple forms, that is, complexes, active and pro-forms of neutrophilic and mesenchymal-type MMP-8, and especially 20-27 kDa fragments. The quantity of these fragments was elevated in both localized and generalized forms of periodontitis. Moreover, the tested activators (Td-CTLP, NaOCl and APMA) activated inactive proMMP-8, resulting in fragments of 20-27 kDa, in vitro, and salivary concentrations of T. denticola correlated significantly with salivary levels of fragmented MMP-8. CONCLUSION: The present results indicate that during the development and progression of periodontitis, MMP-8 appears as activated and fragmented, and treponemal proteases most likely play role in this cascade.

Saliva and serum biomarkers in periodontitis and coronary artery disease.

AIM: Matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and myeloperoxidase (MPO) participate in extracellular matrix breakdown both in periodontium and atherosclerotic plaques. We investigated the diagnostic value of serum and saliva biomarkers in periodontitis and acute coronary syndrome (ACS). MATERIALS AND METHODS: The population was PAROGENE (n = 481), a random cohort of patients with an indication for coronary angiography. All patients underwent a clinical and radiographic oral examination. Groups consisting of periodontitis versus non-periodontitis, and ACS versus non-ACS patients were compared. RESULTS: Saliva MMP-8, MMP-9 and MPO provided significant area-under-curve (AUC) values for periodontitis, 0.69 (<0.001), 0.66 (<0.001) and 0.68 (<0.001), respectively. Serum MMP-8, MMP-9 and MPO levels distinguished ACS from non-ACS patients with AUCs of 0.73 (<0.001), 0.58 (0.03) and 0.68 (<0.001), respectively. Periodontitis confounded the use of serum MMP-9 in diagnostics of ACS. Cardiac status complicated the use of saliva TIMP-1 in periodontal diagnostics. Saliva biomarkers could not be used in ACS diagnosis, and serum biomarkers were not useful in diagnosis of periodontitis. CONCLUSIONS: MMP-8, MMP-9, TIMP-1and MPO are valuable biomarkers for both ACS and periodontitis, but the selection of sample material is crucial; serum is suitable for ACS and saliva for periodontal diagnostic aid.

Aggregatibacter actinomycetemcomitans serotypes associate with periodontal and coronary artery disease status.

AIM: We investigated the association between the Aggregatibacter actinomycetemcomitans serotypes, periodontal status and coronary artery disease (CAD). MATERIALS AND METHODS: The study population included 497 patients who underwent coronary angiography, and clinical oral examination. Quantitative polymerase chain reaction assays were designed to identify the serotypes from saliva samples. RESULTS: Aggregatibacter actinomycetemcomitans serotype frequencies were as follows: serotype "c" 35.7%, "b" 28.6%, "a" 26.2%, "e" 7.1%, "d" 2.4% and "f" 0%. The subjects with a detectable serotype had less teeth and higher bleeding on probing than those with no serotype. Serotypes "b" and "c" associated with periodontal probing depths and periodontal inflammatory burden. The saliva and subgingival bacterium quantities and serum antibody levels against A. actinomycetemcomitans were highest in patients harbouring serotype "c." Serotypes "b" and "c" were most frequent (59.3%) in patients with CAD (p = .040), and they associated with the risk of stable CAD with an odds ratio of 2.67 (95% confidence interval 1.06-7.44). Also, the severity of CAD (p = .018) associated with serotypes "b" and "c." CONCLUSIONS: Aggregatibacter actinomycetemcomitans serotypes "b" and "c" associate with both periodontal and CAD status. Detectable serotypes associate with the quantity and the serology of the bacterium emphasizing both local and systemic effect of the A. actinomycetemcomitans serotypes.

Mediators between oral dysbiosis and cardiovascular diseases.

Clinical periodontitis is associated with an increased risk for cardiovascular diseases (CVDs) through systemic inflammation as the etiopathogenic link. Whether the oral microbiota, especially its quality, quantity, serology, and virulence factors, plays a role in atherogenesis is not clarified. Patients with periodontitis are exposed to bacteria and their products, which have access to the circulation directly through inflamed oral tissues and indirectly (via saliva) through the gastrointestinal tract, resulting in systemic inflammatory and immunologic responses. Periodontitis is associated with persistent endotoxemia, which has been identified as a notable cardiometabolic risk factor. The serology of bacterial biomarkers for oral dysbiosis is associated with an increased risk for subclinical atherosclerosis, prevalent and future coronary artery disease, and incident and recurrent stroke. In addition to species-specific antibodies, the immunologic response includes persistent, cross-reactive, proatherogenic antibodies against host-derived antigens. Periodontitis may affect lipoprotein metabolism at all levels, and all lipoprotein classes are affected. Periodontitis or its bacterial signatures may be involved not only in increased storage of proatherogenic lipids but also in attenuation of the anti-atherogenic processes, thereby putatively increasing the net risk of atherosclerosis. In this review we summarize possible molecular mediators between the dysbiotic oral microbiota and atherosclerotic processes.

Cumulative use of salivary markers with an adaptive design improves detection of periodontal disease over fixed biomarker thresholds.

OBJECTIVE: Aim was to analyze the diagnostic ability of cumulative risk score (CRS), which uses salivary levels of Porphyromonas gingivalis, interleukin (IL)-1ß, and matrix metalloproteinase (MMP)-8 in an adaptive design, compared to previously reported thresholds of each marker alone. MATERIALS AND METHODS: Oral and general health information of 463 participants were included in the analysis. Having the percentage of bleeding on probing (BOP) > 25%, having at least two sites with probing pocket depth (PPD) of 4-5 mm or having at least one tooth with alveolar bone loss (ABL) of at least 1/3 of the root length were accepted as outcome variables. Being above the salivary threshold concentrations of P. gingivalis, IL-1ß, and MMP-8 and CRS values were used as explanatory variables. Receiver operating characteristics (ROC) producing an area under the curve (AUC) and multinomial regression analysis were used in statistical analysis. RESULTS: CRS provided AUCs larger than any other tested biomarker threshold. Sensitivity and specificity of CRS for detecting clinical markers of periodontitis were acceptable, and a strong association was observed between the highest CRS score and having at least two sites with PPD of 4-5 mm. CONCLUSION: CRS brings additional power over fixed thresholds of single biomarkers in detecting periodontitis.

Lipopolysaccharide, a possible molecular mediator between periodontitis and coronary artery disease.

AIM: We aimed to study how lipopolysaccharide (LPS) in saliva and serum associates with each other, periodontal microbial burden, periodontitis and coronary artery disease (CAD). MATERIALS AND METHODS: The used Parogene cohort comprised N = 505 Finnish adults. Coronary diagnosis was acquired by coronary angiography, and the main outcomes were as follows: no significant CAD (n = 123), stable CAD (n = 184) and acute coronary syndrome (n = 169). Periodontitis was defined according to clinical and radiographic examinations. Levels for 75 strains of subgingival bacteria were determined by checkerboard DNA-DNA hybridization. Saliva and serum LPS activity was analysed by Limulus amebocyte lysate assay. RESULTS: The level of 11 bacterial strains, which were mainly oral and respiratory Gram-negative species, associated with salivary LPS levels in an age- and gender-adjusted linear regression. A total of 4.9% of the serum LPS, that is endotoxemia, variation was explainable by saliva LPS among patients with periodontitis (n = 247, R2  = .049, Pearson's r = .222, p < .001). Endotoxemia associated with stable CAD in a confounder adjusted multinomial logistic regression model (OR 1.99, 95% CI 1.04-3.81, p = .039, 3rd tertile). CONCLUSIONS: In particular in periodontitis patients, subgingival microbial burden contributes to endotoxemia. LPS is a possible molecular mediator between periodontitis and CAD.