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Background The enterosalivary nitrate-nitrite-nitric oxide (NO3-NO2-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO2, NO, or ammonia [NH3]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH3 summary ratio was inversely associated with a -0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

Periodontitis affects up to 50% of individuals worldwide, and 8.5% are diagnosed with diabetes. The high-comorbidity rate of these diseases may suggest, at least in part, a shared etiology and pathophysiology. Changes in oral microbial communities have been documented in the context of severe periodontitis and diabetes, both independently and together. However, much less is known about the early oral microbial markers of these diseases. We used a subset of the ORIGINS project dataset, which collected detailed periodontal and cardiometabolic information from 787 healthy individuals, to identify early microbial markers of periodontitis and its association with markers of cardiometabolic health. Using state-of-the-art compositional data analysis tools, we identified the log-ratio of Treponema to Corynebacterium bacteria to be a novel Microbial Indicator of Periodontitis (MIP), and found that this MIP correlates with poor periodontal health and cardiometabolic markers early in disease pathogenesis in both subgingival plaque and saliva.

Fusobacterium nucleatum (Fn) is a Gram-negative oral commensal, prevalent in various human diseases. It is unknown how this common commensal converts to a rampant pathogen. We report that Fn secretes an adhesin (FadA) with amyloid properties via a Fap2-like autotransporter to enhance its virulence. The extracellular FadA binds Congo Red, Thioflavin-T, and antibodies raised against human amyloid β42. Fn produces amyloid-like FadA under stress and disease conditions, but not in healthy sites or tissues. It functions as a scaffold for biofilm formation, confers acid tolerance, and mediates Fn binding to host cells. Furthermore, amyloid-like FadA induces periodontal bone loss and promotes CRC progression in mice, with virulence attenuated by amyloid-binding compounds. The uncleaved signal peptide of FadA is required for the formation and stability of mature amyloid FadA fibrils. We propose a model in which hydrophobic signal peptides serve as "hooks" to crosslink neighboring FadA filaments to form a stable amyloid-like structure. Our study provides a potential mechanistic link between periodontal disease and CRC and suggests anti-amyloid therapies as possible interventions for Fn-mediated disease processes.

INTRODUCTION: We examined the association of clinical, microbiological, and host response features of periodontitis with MRI markers of atrophy/cerebrovascular disease in the Washington Heights Inwood Columbia Aging Project (WHICAP) Ancillary Study of Oral Health. METHODS: We analyzed 468 participants with clinical periodontal data, microbial plaque and serum samples, and brain MRIs. We tested the association of periodontitis features with MRI features, after adjusting for multiple risk factors for Alzheimer's disease/Alzheimer's disease‐related dementia (AD/ADRD). RESULTS: In fully adjusted models, having more teeth was associated with lower odds for infarcts, lower white matter hyperintensity (WMH) volume, higher entorhinal cortex volume, and higher cortical thickness. Higher extent of periodontitis was associated with lower entorhinal cortex volume and lower cortical thickness. Differential associations emerged between colonization by specific bacteria/serum antibacterial IgG responses and MRI outcomes. DISCUSSION: In an elderly cohort, clinical, microbiological, and serological features of periodontitis were associated with MRI findings related to ADRD risk. Further investigation of causal associations is warranted. [ABSTRACT FROM AUTHOR]

Background: A new periodontitis classification was recently introduced involving multidimensional staging and grading. The aim of the study was to assess if individuals well-trained in periodontics consistently used the new classification for patients with severe periodontitis. The secondary goal was to identify "gray zones" related to classifications.Methods: Participants (raters) individually classified 10 pre-selected severe periodontitis cases using the 2017 World Workshop classification. An internet case-based study was conducted after inviting members from American Academy of Periodontology and European Federation of Periodontology. Gold-standard diagnoses were determined by five experts who developed the new periodontitis classification. Inter-reliability agreement among raters was assessed using Fleiss Kappa index with the jackknife method for linearly weighted kappa calculations. McNemar test was used to determine symmetry between raters and gold-standard panel.Results: A total of 103 raters participated and classified nine clinical cases. Fleiss Kappa values showed moderate inter-examiner consistency among raters for stage (K value: 0.49; 95% CI, 0.19 to 0.79), grade (K value: 0.50; 95% CI, 0.30 to 0.70) and extent (K value: 0.51; 95% CI, 0.23 to 0.77). When analyzed as composite (stage, grade, extent) a moderate inter-reliability was present among raters, k = 0.479 (K value: 0.47; 95% CI, 0.442 to 0.515). Agreement between raters and gold-standard panel was staging 76.6%; grading 82%; and extent 84.8%. In six of nine cases 77% to 99% of raters consistently agreed with gold-standard panel, and the other three cases had gray zone factors that reduced rater consistency.Conclusions: Clinicians trained in the 2017 World Workshop periodontitis classification demonstrated moderate concordance in classifying nine severe periodontitis cases, and in six of nine cases raters consistently agreed with the gold-standard panel. [ABSTRACT FROM AUTHOR]

The premise for the oral-systemic diseases relationship dates to the early 20th century with the introduction of the focal infection theory that posited that oral disease affects overall health and wellbeing. While the biological plausibility for the link has been supported by experimental animal models and observational studies in humans, findings from interventional studies in which periodontal therapy failed to alleviate systemic health outcomes have often been interpreted as evidence against periodontitis contribution to the etiology of systemic health conditions. One concept of causation assumes a one-to-one correspondence between cause and effect. Nevertheless, common chronic diseases to which periodontitis is associated have multifactorial etiologies. This commentary provides an overview of Rothman's "sufficient cause" model as a framework for consideration of the oral-systemic diseases link. [ABSTRACT FROM AUTHOR]

Background: Peri-implantitis is a challenging condition to manage and is frequently treated using non-surgical debridement. The local delivery of antimicrobial agents has demonstrated benefit in mild to moderate cases of peri-implantitis. This study compared the safety and efficacy of chlorhexidine gluconate 2.5 mg chip (CHX chips) as an adjunctive treatment to subgingival debridement in patients afflicted with peri-implantitis.Methods: A multicenter, randomized, single-blind, two-arm, parallel Phase-3 study was conducted. Peri-implantitis patients with implant pocket depths (IPD) of 5-8 mm underwent subgingival implant surface debridement followed by repeated bi-weekly supragingival plaque removal and chlorhexidine chips application (ChxC group) for 12 weeks, or similar therapy but without application of ChxC (control group). All patients were followed for 24 weeks. Plaque and gingival indices were measured at every visit whereas IPD, recession, and bleeding on probing were assessed at 8, 12, 16, 24 week.Results: A total of 290 patients were included: 146 in the ChxC group and 144 in the control. At 24 weeks, a significant reduction in IPD (P = 0.01) was measured in the ChxC group (1.76 ± 1.13 mm) compared with the control group (1.54 ± 1.13 mm). IPD reduction of ≥2 mm was found in 59% and 47.2% of the implants in the ChxC and control groups, respectively (P = 0.03). Changes in gingival recession (0.29 ± 0.68 mm versus 0.15 ± 0.55 mm, P = 0.015) and relative attachment gain (1.47 ± 1.32 mm and 1.39 ± 1.27 mm, P = 0.0017) were significantly larger in the ChxC group. Patients in the ChxC group that were < 65 years exhibited significantly better responses (P < 0.02); likewise, non-smokers had similarly better response (P < 0.02). Both protocols were well tolerated, and no severe treatment-related adverse events were recorded throughout the study.Conclusions: Patients with peri-implantitis that were treated with an intensive treatment protocol of bi-weekly supragingival plaque removal and local application of chlorhexidine chips had greater mean IPD reduction and greater percentile of sites with IPD reduction of ≥2 mm as compared with bi-weekly supra-gingival plaque removal. [ABSTRACT FROM AUTHOR]

Background: There is a sparsity of data describing the periodontal microbiome in elderly individuals. We analyzed the association of subgingival bacterial profiles and clinical periodontal status in a cohort of participants in the Washington Heights-Inwood Columbia Aging Project (WHICAP).Methods: Dentate individuals underwent a full-mouth periodontal examination at six sites/tooth. Up to four subgingival plaque samples per person, each obtained from the mesio-lingual site of the most posterior tooth in each quadrant, were harvested and pooled. Periodontal status was classified according to the Centers for Disease Control/American Academy of Periodontology (CDC/AAP) criteria as well as based on the percentage of teeth/person with pockets ≥4 mm deep. Bacterial DNA was isolated and was processed and analyzed using Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS). Differential abundance across the periodontal phenotypes was calculated using the R package DESeq2. α- and β-diversity metrics were calculated using DADA2-based clustering.Results: The mean age of the 739 participants was 74.5 years, and 32% were male. Several taxa including Sneathia amnii-like sp., Peptoniphilaceae [G-1] bacterium HMT 113, Porphyromonas gingivalis, Fretibacterium fastidiosum, Filifactor alocis, and Saccharibacteria (TM7) [G-1] bacterium HMT 346 were more abundant with increasing severity of periodontitis. In contrast, species such as Veillonella parvula, Veillonella dispar, Rothia dentocariosa, and Lautropia mirabilis were more abundant in health. Microbial diversity increased in parallel with the severity and extent of periodontitis.Conclusions: The observed subgingival bacterial patterns in these elderly individuals corroborated corresponding findings in younger cohorts and were consistent with the concept that periodontitis is associated with perturbations in the resident microbiome. [ABSTRACT FROM AUTHOR]

Background: Successful dissemination of the new classification of periodontitis is facilitated by emphasis on the basic ground rules, clarification of ambiguities, and identification of "gray zones" where thoughtful application of the guidelines by an informed, experienced clinician is paramount to arrive at a correct Stage and Grade.Methods: Highlighted ground rules are (1) Stage is a patient-based, not a tooth-based concept, therefore, a single Stage is assigned per patient; (2) Stage can shift upward over time, if the periodontal status deteriorates, but the initially assigned Stage is retained even after improvement post-therapy; (3) the complexity factors that determine Stage must be evaluated collectively, not in isolation, to arrive at a clinically meaningful assessment; (4) a single Grade is assigned to a patient based on a deliberate evaluation of the "biological fabric" of the case, in terms of history of/risk for further progression, interplay of risk factors, and the two-way effects of periodontitis or its treatment on general health; (v) shift of Grade over time is possible towards either direction, after thorough, collective, evaluation of changes in the above parameters. Exemplified gray zones include a radiographically intact patient with minimal attachment loss in older age; presence of "frank" periodontitis affecting a single tooth; and assessment of factors that do/do not lead to increased complexity of therapy.Conclusion: Differentiating between Stage I/II versus Stage III/IV periodontitis is relatively uncomplicated; further distinction between Stages and correct assignment of Grade requires nuanced, thorough interpretation of a broad array of findings by a knowledgeable clinician. [ABSTRACT FROM AUTHOR]

A classification scheme for periodontal and peri‐implant diseases and conditions is necessary for clinicians to properly diagnose and treat patients as well as for scientists to investigate etiology, pathogenesis, natural history, and treatment of the diseases and conditions. This paper summarizes the proceedings of the World Workshop on the Classification of Periodontal and Peri‐implant Diseases and Conditions. The workshop was co‐sponsored by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) and included expert participants from all over the world. Planning for the conference, which was held in Chicago on November 9 to 11, 2017, began in early 2015. An organizing committee from the AAP and EFP commissioned 19 review papers and four consensus reports covering relevant areas in periodontology and implant dentistry. The authors were charged with updating the 1999 classification of periodontal diseases and conditions and developing a similar scheme for peri‐implant diseases and conditions. Reviewers and workgroups were also asked to establish pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use of the new classification. All findings and recommendations of the workshop were agreed to by consensus. This introductory paper presents an overview for the new classification of periodontal and peri‐implant diseases and conditions, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification. Changes to the 1999 classification are highlighted and discussed. Although the intent of the workshop was to base classification on the strongest available scientific evidence, lower level evidence and expert opinion were inevitably used whenever sufficient research data were unavailable. The scope of this workshop was to align and update the classification scheme to the current understanding of periodontal and peri‐implant diseases and conditions. This introductory overview presents the schematic tables for the new classification of periodontal and peri‐implant diseases and conditions and briefly highlights changes made to the 1999 classification. It cannot present the wealth of information included in the reviews, case definition papers, and consensus reports that has guided the development of the new classification, and reference to the consensus and case definition papers is necessary to provide a thorough understanding of its use for either case management or scientific investigation. Therefore, it is strongly recommended that the reader use this overview as an introduction to these subjects. Accessing this publication online will allow the reader to use the links in this overview and the tables to view the source papers (Table 1). [ABSTRACT FROM AUTHOR]

A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi‐dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history‐based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic‐periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination. [ABSTRACT FROM AUTHOR]

Objective: We used epidemiologic data of clinical periodontal status from two population‐based samples in two countries, United States and Germany, to examine 1) the impact of age on the relative contribution of recession and pocketing on the distribution of clinical attachment loss, and 2) whether it is feasible to define age‐dependent thresholds for severe periodontitis. Methods: The analytical sample was based on persons aged ≥30 and included 10,713 individuals in the United States, participants in NHANES 2009 to 2014, and 3,071 individuals in Pomerania, Germany, participants in the SHIP‐Trend 2008 to 2012. NHANES used a full‐mouth examination protocol to collect data on recession (R), pocket depth (PD) and clinical attachment loss (CAL) for six sites/tooth on a maximum of 28 teeth; SHIP‐Trend used a half‐mouth examination at four sites/tooth. In both samples, percentile distributions of mean CAL/person were generated for each 5‐year age interval. Age‐dependent thresholds defining the upper quintile of mean CAL were calculated for both samples. The topographic intraoral distribution of CAL and the relative contribution of R and PD on CAL was assessed. Results: Mean CAL increased linearly with age in both samples and was higher in SHIP‐Trend than NHANES across the age spectrum. In contrast, mean PD was constant across age groups in both populations. R contributed increasingly to CAL with age, especially after 45 to 49 years. Upper quintile mean CAL thresholds in NHANES were < 3 mm for ages up to 39 years, and under 3.58 mm in all other age groups. Corresponding values in SHIP‐Trend were also < 3 mm in ages up to 39 years but increased linearly with age up to 7.21 mm for ages ≥75 years. Conclusions: Despite substantial differences in the overall severity of attachment loss between the two samples, common patterns of CAL and of the relative contribution of R and PD to CAL with increasing age were identified. Although periodontitis severity may vary in different populations, empirical evidence‐driven definitions of CAL thresholds signifying disproportionate severity of periodontitis by age are feasible. [ABSTRACT FROM AUTHOR]

A classification scheme for periodontal and peri-implant diseases and conditions is necessary for clinicians to properly diagnose and treat patients as well as for scientists to investigate etiology, pathogenesis, natural history, and treatment of the diseases and conditions. This paper summarizes the proceedings of the World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. The workshop was co-sponsored by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) and included expert participants from all over the world. Planning for the conference, which was held in Chicago on November 9 to 11, 2017, began in early 2015. An organizing committee from the AAP and EFP commissioned 19 review papers and four consensus reports covering relevant areas in periodontology and implant dentistry. The authors were charged with updating the 1999 classification of periodontal diseases and conditions and developing a similar scheme for peri-implant diseases and conditions. Reviewers and workgroups were also asked to establish pertinent case definitions and to provide diagnostic criteria to aid clinicians in the use of the new classification. All findings and recommendations of the workshop were agreed to by consensus. This introductory paper presents an overview for the new classification of periodontal and peri-implant diseases and conditions, along with a condensed scheme for each of four workgroup sections, but readers are directed to the pertinent consensus reports and review papers for a thorough discussion of the rationale, criteria, and interpretation of the proposed classification. Changes to the 1999 classification are highlighted and discussed. Although the intent of the workshop was to base classification on the strongest available scientific evidence, lower level evidence and expert opinion were inevitably used whenever sufficient research data were unavailable. The scope of this workshop was to align and update the classification scheme to the current understanding of periodontal and peri-implant diseases and conditions. This introductory overview presents the schematic tables for the new classification of periodontal and peri-implant diseases and conditions and briefly highlights changes made to the 1999 classification. It cannot present the wealth of information included in the reviews, case definition papers, and consensus reports that has guided the development of the new classification, and reference to the consensus and case definition papers is necessary to provide a thorough understanding of its use for either case management or scientific investigation. Therefore, it is strongly recommended that the reader use this overview as an introduction to these subjects. Accessing this publication online will allow the reader to use the links in this overview and the tables to view the source papers (Table 1). [ABSTRACT FROM AUTHOR]

The aim of this study was to use electronic health care records (EHRs) to examine retrospectively the incidence of and attributes associated with dental implant failures necessitating implant removal in a large cohort of patients treated in the student clinics of a U.S. dental school over three and a half years. EHRs were searched for all patients who received dental implants between July 1, 2011, and December 31, 2014. Characteristics of patients and implants that were actively removed due to irrevocable failure of any etiology ("failure cohort") during this period were compared to those of all other patients who received dental implants during the same time frame ("reference cohort"). Differences in the frequency distribution of various characteristics between the failure and reference cohorts were compared. Of a total 6,129 implants placed in 2,127 patients during the study period, 179 implants (2.9%) in 120 patients (5.6%) were removed. In the multivariate analysis, presence of a removable (OR=2.86) or fixed temporary prosthesis (OR=3.71) was statistically significantly associated with increased risk for implant failure. In contrast, antibiotic coverage (pre- and post-surgery OR=0.16; post-surgery only OR=0.38) and implants of certain manufacturers were associated with lower risk of implant failure. In this sizeable cohort of patients receiving care in dental student clinics, the review of EHRs facilitated identification of multiple variables associated with implant failure resulting in removal; however, these findings do not suggest causative relationships. The adopted analytical approach can enhance quality assurance measures and may contribute to the identification of true risk factors for dental implant failure. [ABSTRACT FROM AUTHOR]

Background: Recreational use of cannabis, following its legalization in some countries, poses emergent oral and periodontal health concerns. The objective of this study is to examine the relationship between frequent recreational cannabis (FRC) (marijuana and hashish) use and periodontitis prevalence among adults in the United States.Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2011 to 2012 were analyzed. Primary outcome (periodontitis) was defined using the Centers for Disease Control and Prevention/American Academy of Periodontology classification as well as continuous measurements of probing depth (PD) and clinical attachment loss (AL). Exposure of interest was self-reported cannabis use, defined as "FRC use" versus "non-FRC use." Bivariate and multivariable regression models were performed using the entire analytical sample (model 1) as well as those who had never used tobacco (never-users) (model 2).Results: Of 1,938 participants with available cannabis use data and essential covariates, 26.8% were FRC users. Mean number of sites per participant with PD ≥4, ≥6, and ≥8 mm and AL ≥3, ≥5, and ≥8 mm was significantly higher among FRC users than among non-FRC users (mean difference in number of PD sites: 6.9, 5.6, and 5.6; P <0.05; mean difference in number of AL sites: 12.7, 7.6, and 5.6; P <0.05). Average AL was higher among FRC users than among non-FRC users (1.8 versus 1.6 mm; P = 0.004). Bivariate analysis revealed positive (harmful) association between FRC use and severe periodontitis in the entire sample (odds ratio [OR]: 1.7, 95% confidence interval [CI]: 1.3 to 2.4; P = 0.002) as well as in never-smokers (OR: 2.0, 95% CI: 1.2 to 3.5; P = 0.01). This association was retained in multivariable models adjusted for demographics (age, sex, race/ethnicity, and income level), alcohol and tobacco use, diabetes mellitus, and past periodontal treatment (model 1: adjusted OR [aOR]: 1.4, 95% CI: 1.1 to 1.9; P = 0.07; model 2: aOR: 1.9, 95% CI: 1.1 to 3.2; P = 0.03).Conclusion: FRC use is associated with deeper PDs, more clinical AL, and higher odds of having severe periodontitis. [ABSTRACT FROM AUTHOR]

Analytic approaches confined to fold-change comparisons of gene expression patterns between states of health and disease are unable to distinguish between primary causal disease drivers and secondary noncausal events. Genome-wide reverse engineering approaches can facilitate the identification of candidate genes that may distinguish between causal and associative interactions and may account for the emergence or maintenance of pathologic phenotypes. In this work, we used the algorithm for the reconstruction of accurate cellular networks (ARACNE) to analyze a large gene expression profile data set (313 gingival tissue samples from a cross-sectional study of 120 periodontitis patients) obtained from clinically healthy (n = 70) or periodontitis-affected (n = 243) gingival sites. The generated transcriptional regulatory network of the gingival interactome was subsequently interrogated with the master regulator inference algorithm (MARINA) and gene expression signature data from healthy and periodontitis-affected gingiva. Our analyses identified 41 consensus master regulator genes (MRs), the regulons of which comprised between 25 and 833 genes. Regulons of 7 MRs (HCLS1, ZNF823, XBP1, ZNF750, RORA, TFAP2C, and ZNF57) included >500 genes each. Gene set enrichment analysis indicated differential expression of these regulons in gingival health versus disease with a type 1 error between 2% and 0.5% and with >80% of the regulon genes in the leading edge. Ingenuity pathway analysis showed significant enrichment of 36 regulons for several pathways, while 6 regulons (those of MRs HCLS1, IKZF3, ETS1, NHLH2, POU2F2, and VAV1) were enriched for >10 pathways. Pathways related to immune system signaling and development were the ones most frequently enriched across all regulons. The unbiased analysis of genome-wide regulatory networks can enhance our understanding of the pathobiology of human periodontitis and, after appropriate validation, ultimately identify target molecules of diagnostic, prognostic, or therapeutic value. [ABSTRACT FROM AUTHOR]

Periodontitis and type 2 diabetes mellitus are known to be associated. The relationship between periodontal microbiota and early diabetes risk has not been studied. We investigated the association between periodontal bacteria and prediabetes prevalence among diabetes-free adults. ORIGINS (the Oral Infections, Glucose Intolerance and Insulin Resistance Study) cross sectionally enrolled 300 diabetes-free adults aged 20 to 55 y (mean ± SD, 34 ± 10 y; 77% female). Prediabetes was defined as follows: 1) hemoglobin A1c values ranging from 5.7% to 6.4% or 2) fasting plasma glucose ranging from 100 to 125 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species were assessed at baseline, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Actinomyces naeslundii. Full-mouth clinical periodontal examinations were performed, and participants were defined as having no/mild periodontitis vs. moderate/severe periodontitis per the definition of the Centers for Disease Control and Prevention / American Academy of Periodontology. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Prevalence ratios and 95% confidence intervals for third vs. first tertiles are presented. All analyses were adjusted for cardiometabolic risk factors. All results presented currently arise from the baseline cross section. Prediabetes prevalence was 18%, and 58% of participants had moderate/severe periodontitis. Prevalence ratios (95% confidence intervals) summarizing associations between bacterial levels and prediabetes were as follows: A. actinomycetemcomitans, 2.48 (1.34, 4.58), P = 0.004; P. gingivalis, 3.41 (1.78, 6.58), P = 0.0003; T. denticola, 1.99 (0.992, 4.00), P = 0.052; T. forsythia, 1.95 (1.0, 3.84), P = 0.05; A. naeslundii, 0.46 (0.25, 0.85), P = 0.01. The prevalence ratio for prediabetes among participants with moderate/severe vs. no/mild periodontitis was 1.47 (0.78, 2.74), P = 0.23. Higher colonization levels of specific periodontal microbiota are associated with higher prediabetes prevalence among diabetes-free adults. [ABSTRACT FROM AUTHOR]

Background: Several biologically plausible mechanisms have been proposed to mediate the association between periodontitis and atherosclerotic vascular disease (AVD), including adverse effects on vascular endothelial function. Circulating endothelial progenitor cells (cEPCs) are known to contribute to vascular repair, but limited data are available regarding the relationship between cEPC levels and periodontitis. The aims of this cross-sectional study are to investigate the levels of hemangioblastic and monocytic cEPCs in patients with periodontitis and periodontally healthy controls and to associate cEPC levels with the extent and severity of periodontitis. Methods: A total of 112 individuals (56 patients with periodontitis and 56 periodontally healthy controls, aged 26 to 65 years; mean age: 43 years) were enrolled. All participants underwent a full-mouth periodontal examination and provided a blood sample. Hemangioblastic cEPCs were assessed using flow cytometry, and monocytic cEPCs were identified using immunohistochemistry in cultured peripheral blood mononuclear cells. cEPC levels were analyzed in the entire sample, as well as in a subset of 50 pairs of patients with periodontitis/periodontally healthy controls, matched with respect to age, sex, and menstrual cycle. Results: Levels of hemangioblastic cEPCs were approximately 2.3-fold higher in patients with periodontitis than periodontally healthy controls, after adjustments for age, sex, physical activity, systolic blood pressure, and body mass index (P = 0.001). A non-significant trend for higher levels of monocytic cEPCs in periodontitis was also observed. The levels of hemangioblastic cEPCs were positively associated with the extent of bleeding on probing, probing depth, and clinical attachment loss. Hemangioblastic and monocytic cEPC levels were not correlated (Spearman correlation coefficient 0.03, P= 0.77), suggesting that they represent independent populations of progenitor cells. Conclusion: These findings further support the notion that oral infections have extraoral effects and document that periodontitis is associated with a mobilization of EPCs from the bone marrow, apparently in response to systemic inflammation and endothelial injury. [ABSTRACT FROM AUTHOR]

Background: The authors revisited the 1999 International Workshop postulate of robust serum antibody responses to infecting agents in localized aggressive periodontitis (LAgP) and weak responses in generalized aggressive periodontitis (GAgP). Antibody responses were further examined in localized and generalized chronic periodontitis (LCP and GCP). Methods: The study includes 119 patients (60 males and 59 females, aged 11 to 76 years), 18 with LAgP, 37 with GAgP, 37 with LCP, and 27 with GCP. Multiple subgingival plaque samples/patient (1,057 in total) were analyzed with respect to 11 bacterial species using checkerboard DNA-DNA hybridizations, and serum immunoglobulin (Ig)G levels were measured against the same bacteria using checkerboard immunoblotting. Further, infection ratios (antibody level over the average bacterial colonization by the homologous species) were computed for each patient. Comparisons of bacterial colonization, serum IgG levels, and infection ratios were made across the diagnostic categories using multivariable linear regression models adjusting for age and race/ethnicity. Results: There were no statistically significant differences in serum IgG levels to Aggregatibacter actinomycetemcomitans among the four diagnostic categories. IgG levels to several species, including Porphyromonas gingivalis, Treponema denticola, and Campylobacter rectus, were highest in patients with GAgP and significantly different from LCP and GCP, but not from LAgP. Comparisons based on infection ratios showed no statistically significant differences for any species between GAgP and LAgP. Conclusion: This study provides evidence against the 1999 Workshop's postulate of weak serum antibody responses in patients with GAgP and shows that serum IgG responses in GAgP are comparable to those in LAgP, but higher than in GCP or LCP for several species. [ABSTRACT FROM AUTHOR]