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Several serum inflammatory biomarkers have been associated with blood pressure and hypertension prevalence in cross-sectional studies. Few of these associations have been evaluated prospectively. We examined associations for 10 serum inflammatory biomarkers with incident hypertension among 471 postmenopausal women (mean age = 65) in the Buffalo OsteoPerio Study. Concentrations of C-reactive protein, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, adiponectin, and leptin were measured using multiplexed sandwich immunoassays on fasting serum samples collected at baseline (1997-2001). Incident hypertension (195 cases) was defined as physician-diagnosed hypertension and treatment with medication identified on annual mailed health surveys during follow-up (mean 10 years). Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between log-transformed biomarkers (per 1-SD) and hypertension. When adjusted for age, leptin was significantly associated with hypertension risk (HR = 1.55, 95% CI: 1.04, 2.29), however, the association was attenuated and not significant after adjustment for demographic and lifestyle factors, including BMI. Significant (P < 0.10) interactions were observed for smoking (never, ever) with CRP (HR: never, 1.31; ever, 0.91; P = 0.06) and MCP-1 (HR: never, 0.59; ever, 5.11; P = 0.004); for BMI (

Diabetes mellitus is a group of metabolic disorders with high mortality and morbidity associated with complications such as cardiovascular disease, kidney disease, and stroke. The prevalence of diabetes is 9.4% in US adults, and prevalence increases markedly with age, with 1 in 4 adults aged ≥65 years affected by diabetes. The estimated number of adults with type 2 diabetes globally almost tripled between 2002 and 2017, reflecting increases seen in the USA and elsewhere. This increase raises concerns about the increased morbidity and mortality associated with the complications of diabetes, including periodontal disease and tooth loss. There is a reciprocal adverse relationship between diabetes and periodontal disease, with diabetes as a major risk factor for periodontal disease, and in those patients with diabetes who also have periodontal disease then there are adverse effects on glycemic control and complications such as cardiovascular disease and end stage renal disease. In this review, those studies detailing the adverse effects of periodontal disease and diabetes will be discussed. Also, evidence is accumulating that periodontitis may play a role in increasing the incidence of new cases of type 2 diabetes, and possibly gestational diabetes. Of course, these studies need to be expanded to better understand the effects of periodontitis on diabetes glycemic control, complications, prediabetes, and the incidence of new cases. However, given the tremendous burden of diabetes on society, the dental profession should be proactive in preventing and treating periodontal disease, not only to preserve the dentition, but also to minimize the adverse effects of periodontitis on diabetes and its complications.

Epidemiologic and cancer control studies on the association of periodontal disease and cancer risk mostly suggest a positive association with overall cancer risk and certain specific types of cancer. These findings are generally consistent among cross‐sectional and longitudinal studies. In this paper, we review epidemiologic studies and current knowledge on periodontal disease and cancer, with a focus on those studies conducted in the years following the Joint European Federation of Periodontology/American Academy of Periodontology Workshop on “Periodontitis and Systemic Diseases” in November 2012. This review also explores the role of chronic inflammation as a biologically plausible mechanistic link between periodontal disease and risk of cancer. Furthermore, it highlights studies that have examined the potential importance of certain periodontal pathogens in this association.

The most important development in the epidemiology of periodontitis in the USA during the last decade is the result of improvements in survey methodologies and statistical modeling of periodontitis in adults. Most of these advancements have occurred as the direct outcome of work by the joint initiative known as the Periodontal Disease Surveillance Project by the Centers for Disease Control and Prevention and the American Academy of Periodontology that was established in 2006. This report summarizes some of the key findings of this important initiative and its impact on our knowledge of the epidemiology of periodontitis in US adults. This initiative first suggested new periodontitis case definitions for surveillance in 2007 and revised them slightly in 2012. This classification is now regarded as the global standard for periodontitis surveillance and is used worldwide. First, application of such a standard in reporting finally enables results from different researchers in different countries to be meaningfully compared. Second, this initiative tackled the concern that prior national surveys, which used partial-mouth periodontal examination protocols, grossly underestimated the prevalence of periodontitis of potentially more than 50%. Consequently, because previous national surveys significantly underestimated the true prevalence of periodontitis, it is not possible to extrapolate any trend in periodontitis prevalence in the USA over time. Any difference calculated may not represent any actual change in periodontitis prevalence, but rather is a consequence of using different periodontal examination protocols. Finally, the initiative addressed the gap in the need for state and local data on periodontitis prevalence. Through the direct efforts of the Centers for Disease Control and Prevention and the American Academy of Periodontology initiative, full-mouth periodontal probing at six sites around all nonthird molar teeth was included in the 6 years of National Health and Nutrition Examination Surveys from 2009-2014, yielding complete data for 10 683 dentate community-dwelling US adults aged 30 to 79 years. Applying the 2012 periodontitis case definitions to the 2009-2014 National Health and Nutrition Examination Surveys data, the periodontitis prevalence turned out to be much greater than previously estimated, namely affecting 42.2% of the population with 7.8% of people experiencing severe periodontitis. It was also discovered that only the moderate type of periodontitis is driving the increase in periodontitis prevalence with age, not the mild or the severe types whose prevalence do not increase consistently with age, but remain ~ 10%-15% in all age groups of 40 years and older. The greatest risk for having periodontitis of any type was seen in older people, in males, in minority race/ethnic groups, in poorer and less educated groups, and especially in cigarette smokers. The Centers for Disease Control and Prevention and the American Academy of Periodontology initiative reported, for the first time, the periodontitis prevalence estimated at both local and state levels, in addition to the national level. Also, this initiative developed and validated in field studies a set of eight items for self-reported periodontitis for use in direct survey estimates of periodontitis prevalence in existing state-based surveys. These items were also included in the 2009-2014 National Health and Nutrition Examination Surveys for validation against clinically determined cases of periodontitis. Another novel result of this initiative is that, for the first time, the geographic distribution of practicing periodontists in relation to the geographic distribution of people with severe periodontitis is illustrated. In summary, the precise periodontitis prevalence and distribution among subgroups in the dentate US noninstitutionalized population aged 30-79 years is better understood because of application of valid periodontitis case definitions to full-mouth periodontal examination, in combination with reliable information on demographic and health-related measures. We now can monitor the trend of periodontitis prevalence over time as well as guide public health preventive and intervention initiatives for the betterment of the health of the adult US population.

Background Localized aggressive periodontitis (LAgP) occurs in 2% of African-American adolescents but only 0.15% of white adolescents. First molars and incisors are affected by rapid onset and progression. Methods This nonsystematic critical review evaluated published data for LAgP and chronic periodontitis (CP), focusing on potential differences in epidemiology, microbiology, immunology, genetics, and response to therapy. Results LAgP differs from CP by localization to incisors and first molars, early onset and rapid progression in adolescents and young adults, and a 10-fold higher prevalence in populations of African or Middle Eastern origin, often with strong familial aggregation. The bacterium Aggregatibacter actinomycetemcomitans and hyperresponsive neutrophils are frequently observed. Antibiotic and nonsurgical therapies are highly effective. Conclusions LAgP differs in many ways from the far more common CP that affects older adults. The substantial evidence of dissimilarities summarized in this review strongly supports the classification of LAgP as a distinct form of periodontitis. Practical Implications Classifying LAgP as a distinct subcategory of periodontitis will encourage future research and does not conflict with the newly proposed “staging and grading” system. The silent onset and rapid progression of LAgP make early diagnosis and frequent follow-up with patients essential for effective treatment.

Understanding of the oral microbiome in relation to periodontal disease in older adults is limited. The composition and diversity of the subgingival microflora and their oligotypes in health and levels of periodontal disease were investigated in this study on older postmenopausal women. The 16S rRNA gene was sequenced using the Illumina MiSeq platform in 1,206 women aged 53 to 81 y. Presence and severity of periodontal disease were defined by Centers for Disease Control and Prevention/American Academy of Periodontology criteria. Composition of the microbiome was determined by 16S rRNA amplicon sequencing and the abundance of taxa described by the centered log2-ratio (CLR) transformed operational taxonomic unit (OTU) values. Differences according to periodontal disease status were determined by analysis of variance with Bonferroni correction. Bacteria oligotypes associated with periodontal disease and health were determined by minimum entropy decomposition and their functions estimated in silico using PICRUSt. Prevalence of none/mild, moderate, and severe periodontal disease was 25.1%, 58.3%, and 16.6%, respectively. Alpha diversity of the microbiome differed significantly across the 3 periodontal disease categories. β-Diversity differed between no/mild and severe periodontal disease, although considerable overlap was noted. Of the 267 bacterial species identified at ≥0.02% abundance, 56 (20.9%) differed significantly in abundance according to periodontal disease status. Significant linear correlations for pocket depth and clinical attachment level with bacterial amounts were observed for several taxa. Of the taxa differing in abundance according to periodontal disease status, 53% had multiple oligotypes appearing to differ between none/mild and severe periodontal disease. Among older women, taxonomic differences in subgingival microbiome composition and diversity were observed in relation to clinical periodontal disease measures. Potential differences in bacterial subspecies (oligotypes) and their function were also identified in periodontal disease compared with health.

OBJECTIVES: A possible role of the oral microbiome, specifically oral nitrate reducing flora, in blood pressure (BP) homeostasis, if proven etiologic in nature, could lead to novel mechanism-based therapy to improve hypertension prevention and control. This cross-sectional study characterized and compared the oral microbiome between four study groups based on BP status among 446 postmenopausal women aged 53-82 years. METHODS: Three study groups were not taking hypertension medication and were separated based on BP, as follows: normal BP (systolic 140 or diastolic > 90; N=42). The forth group consisted of anyone taking hypertension medications, regardless of BP (N=119). Subgingival microbiome composition was determined using 16S rRNA sequencing with the Illumina MiSeq platform. Kruskal-Wallis tests were used to compare species-level relative abundance of bacterial operational taxonomic units across the four groups. RESULTS: Sixty-five bacterial species demonstrated significant differences in relative abundance in women with elevated BP or using hypertension medication as compared to those with normal BP. After correction for multiple testing, two species, Prevotella oral (species 317) and Streptococcus oralis, remained significant and were lower in abundance among women taking antihypertension medications compared to those with normal BP (corrected P

Background Periodontitis is more common and severe in people with diabetes than the general population. We have reported in the Joslin Medalist Study that people with type 1 diabetes of ≥50 years (Medalists) may have endogenous protective factors against diabetic nephropathy and retinopathy. Methods In this cross-sectional study, the prevalence of periodontitis according to the Centers for Disease Control/American Academy of Periodontology classification in a subset (n = 170, mean age = 64.6 ± 6.9 years) of the Medalist cohort, and its associations to various criteria of periodontitis and diabetic complications were assessed. Results The prevalence of severe periodontitis in Medalists was only 13.5% which was lower than reported levels in diabetic patients of similar ages. Periodontal parameters, including bleeding on probing, plaque index, gingival index, and demographic traits, including male sex, chronological age, and age at diagnosis were significantly associated with severity of periodontitis, which did not associate with diabetes duration, hemoglobin A1c (HbA1c), body mass index, and lipid profiles. Random serum C-peptide levels inversely associated with severity of periodontitis (P = 0.03), lower probing depth (P = 0.0002), and clinical attachment loss (P = 0.03). Prevalence of cardiovascular diseases (CVD) and systemic inflammatory markers, plasma interleukin-6 (IL-6), and serum immunoglobulin G titer against Porphyromonas gingivalis positively associated with severity of periodontitis (P = 0.002 and 0.02, respectively). Antibody titer to P. gingivalis correlated positively and significantly with CVD, serum IL-6, and high-sensitivity C-reactive protein. Conclusions Some Medalists could be protected from severe periodontitis even with hyperglycemia. Endogenous protective factors for periodontitis could possibly be related to residual insulin production and lower levels of chronic inflammation.

Atherosclerosis is central to the pathology of cardiovascular diseases, a group of diseases in which arteries become occluded with atheromas that may rupture, leading to different cardiovascular events, such as myocardial infarction or ischemic stroke. There is a large body of epidemiologic and animal model evidence associating periodontitis with atherosclerotic disease, and many potential mechanisms linking these diseases have been elucidated. This chapter will update knowledge on these mechanisms, which generally fall into 2 categories: microbial invasion and infection of atheromas; and inflammatory and immunologic. With respect to the invasion and infection of atheromas, it is well established that organisms from the subgingival biofilm can enter the circulation and lodge in most distant tissues. Bacteremias resulting from oral interventions, and even oral hygiene activities, are well documented. More recently, indirect routes of entry of oral organisms (via phagocytes or dendritic cells) have been described for many oral organisms, into many tissues. Such organisms include the periodontal pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Intracellular survival of these organisms with dissemination to distant sites (The Trojan Horse approach) has been described. Their relative contribution to atheroma formation and progression has been studied mainly in experimental research, with results demonstrating that these organisms can invade endothelial cells and phagocytic cells within the atheroma, leading to pathogenic changes and progression of the atheroma lesion. The second category of mechanisms potentially linking periodontitis to atherosclerosis includes the dumping of inflammatory mediators originating from periodontal lesions into the systemic circulation. These inflammatory mediators, such as C-reactive protein, matrix metalloproteinases, fibrinogen, and other hemostatic factors, would further accelerate atheroma formation and progression, mainly through oxidative stress and inflammatory dysfunction. Moreover, direct effects on lipid oxidation have also been described. In summary, the evidence supports the concept that periodontitis enhances the levels of systemic mediators of inflammation that are risk factors for atherosclerotic diseases.

Severe periodontitis is defined by extensive loss of the tooth attachment apparatus. It is the sixth most common human disease and is estimated to affect 11.2% of the global adult population, hence representing a significant healthcare, social, and economic burden. Since the 1990s, multiple epidemiologic, experimental, and interventional studies have evidenced how periodontitis may also impact systemic health and it has been independently associated with the majority of chronic noncommunicable diseases. The evidence supporting these associations, mainly focusing on diabetes, pregnancy complications, and cardiovascular disease, was thoroughly reviewed in 2012 by an international consensus workshop. In the last 5 years, however, important advances have been made, not only in our understanding of the etiopathogenesis of periodontitis, or concerning the mounting evidence regarding the independent associations between periodontitis, diabetes, and cardiovascular disease, but also with many other systemic diseases including metabolic disease and obesity, rheumatoid arthritis, certain cancers, respiratory diseases, and cognitive disorders including Alzheimer's disease. This review describes these scientific advances by gathering together the existing evidence on the importance and relevance of the associations between periodontitis and many systemic diseases.

Diabetes affects one in 10 adults and periodontal disease affects four in 10 adults in the USA, and they are linked. Individuals with diabetes are more likely to suffer from periodontal disease and periodontal disease affects glycemic control and complications of diabetes. The role of diabetes as a risk factor for periodontal disease and other oral conditions will be discussed in this review. The fact that type 2 diabetes, especially uncontrolled, is a risk factor for periodontal disease has long been recognized. However, the role of type 1 diabetes and gestational diabetes in periodontal risk has recently been described. Also, diabetes as a risk factor for tooth loss has more recently been described and the deleterious effects of tooth loss, especially edentulism, in comparing the diets of patients with diabetes is now fully appreciated. From longitudinal studies it is clear that diabetes often precedes periodontitis and, hence, may contribute to the causal pathway of periodontitis. Other oral manifestations of diabetes include increased risk of oral and nonoral (vaginal) fungal infections. In patients with diabetes there is often reduced salivary flow associated with diabetes medications and neuropathy affecting the salivary glands. This may lead to increased caries. Burning mouth, resulting from diabetes neuropathy, and taste impairment may also be seen. It has long been known that there is delayed wound healing in patients with diabetes, especially if uncontrolled. Hence, it is critical to achieve good glycemic control before carrying out surgical procedures or dental implant placement in patients with diabetes.

It has become increasingly clear that we live in a symbiotic relationship with microbes within us. We are just beginning to unravel the nature and strength of this relationship and its impact on both physiology and by extension, pathology. While microorganisms have long been known to have carcinogenic potential, their role may have been underestimated. The knowledge of the role of the microbiome in carcinogenesis is rapidly evolving. This evolution has reached a tipping point with current omics technologies used for cataloguing the microbiome. The lung is an organ constantly exposed to the environment. It is now clear that the lung has a distinct microbiome and that this may influence the development of lung cancer. In addition, evidence suggests that this microbiome originates from the oral microbiome. This review summarizes current knowledge about the role of microbiome, especially the oral and lung microbiome in human lung cancer. The goal of the manuscript is to provide a summary of this rapidly evolving field while providing a context of the general role of the microbiome in carcinogenesis. In addition, a primer of the current technology used in evaluating the microbiome is provided to familiarize the practicing clinician with the experimental methods used to generate the information that will likely impact the field of lung cancer.

Several serum inflammatory biomarkers have been associated with blood pressure and hypertension prevalence in cross-sectional studies. Few of these associations have been evaluated prospectively. We examined associations for 10 serum inflammatory biomarkers with incident hypertension among 471 postmenopausal women (mean age = 65) in the Buffalo OsteoPerio Study. Concentrations of C-reactive protein, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, adiponectin, and leptin were measured using multiplexed sandwich immunoassays on fasting serum samples collected at baseline (1997-2001). Incident hypertension (195 cases) was defined as physician-diagnosed hypertension and treatment with medication identified on annual mailed health surveys during follow-up (mean 10 years). Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between log-transformed biomarkers (per 1-SD) and hypertension. When adjusted for age, leptin was significantly associated with hypertension risk (HR = 1.55, 95% CI: 1.04, 2.29), however, the association was attenuated and not significant after adjustment for demographic and lifestyle factors, including BMI. Significant (P 0.10) interactions were observed for smoking (never, ever) with CRP (HR: never, 1.31; ever, 0.91; P = 0.06) and MCP-1 (HR: never, 0.59; ever, 5.11; P = 0.004); for BMI (25, ≥25) with MCP-1(HR:25, 3.45; ≥25, 0.95; P = 0.07); for systolic BP with IL-10 (HR:120, 0.85; 120-139, 1.11; P = 0.07); and for diastolic BP with MCP-1 (HR:80, 1.29; 80-89, 0.84; P = 0.03) and with adiponectin (HR:80, 0.86; 80-89, 1.50; P = 0.03). This study adds needed understanding on prospective associations between several serum inflammatory biomarkers and hypertension risk in older postmenopausal women, among whom hypertension burden is substantial.

Several lines of evidence suggest that gut bacterial microbiota is altered in patients with chronic kidney disease (CKD), though the mechanism of which this dysbiosis takes place is not well understood. Recent studies delineated changes in gut microbiota in both CKD patients and experimental animal models using microarray chips. We present 16S ribosomal RNA gene sequencing of both stool pellets and small bowel contents of C57BL/6J mice that underwent a remnant kidney model and establish that changes in microbiota take place in the early gastrointestinal tract. Increased intestinal urea concentration has been hypothesized as a leading contributor to dysbiotic changes in CKD. We show that urea transporters (UT)-A and UT-B mRNA are both expressed throughout the whole gastrointestinal tract. The noted increase in intestinal urea concentration appears to be independent of UTs’ expression. Urea supplementation in drinking water resulted in alteration in bacterial gut microbiota that is quite different than that seen in CKD. This indicates that increased intestinal urea concentration might not fully explain the CKD- associated dysbiosis.

BACKGROUND Hypertension and periodontal disease are common conditions among postmenopausal women. Periodontal disease has been found associated with hypertension in previous studies, but data in postmenopausal women is limited. METHODS We assessed the cross-sectional associations of clinically measured periodontal disease with prevalent hypertension and measured systolic blood pressure (SBP) among 1341 postmenopausal women enrolled in the Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) study, an ancillary study of the Women's Health Initiative-Observational Study. RESULTS Clinical attachment level (CAL) and number of teeth missing were positively associated with SBP among those not taking antihypertensive medication in crude and multivariable adjusted linear regression models (both P

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations. ispartof: JOURNAL OF PERIODONTOLOGY vol:89 pages:S74-S84 ispartof: location:IL, Chicago status: published

The periodontal pathogen Tannerella forsythia has the unique ability to produce methylglyoxal (MGO), an electrophilic compound which can covalently modify amino acid side chains and generate inflammatory adducts known as advanced glycation endproducts (AGEs). In periodontitis, concentrations of MGO in gingival-crevicular fluid are increased and are correlated with the T. forsythia load. However, the source of MGO and the extent to which MGO may contribute to periodontal inflammation has not been fully explored. In this study we identified a functional homolog of the enzyme methylglyoxal synthase (MgsA) involved in the production of MGO in T. forsythia. While wild-type T.forsythia produced a significant amount of MGO in the medium, a mutant lacking this homolog produced little to no MGO. Furthermore, compared with the spent medium of the T. forsythia parental strain, the spent medium of the T. forsythia mgsA-deletion strain induced significantly lower nuclear factor-kappa B activity as well as proinflammogenic and pro-osteoclastogenic cytokines from THP-1 monocytes. The ability of T. forsythia to induce protein glycation endproducts via MGO was confirmed by an electrophoresis-based collagen chain mobility shift assay. Together these data demonstrated that T. forsythia produces MGO, which may contribute to inflammation via the generation of AGEs and thus act as a potential virulence factor of the bacterium.

A number of studies have associated obesity with altered gut microbiota, although results are discordant regarding compositional changes in the gut microbiota of obese animals. Herein we used a meta-analysis to obtain an unbiased evaluation of structural and functional changes of the gut microbiota in diet-induced obese rodents. The raw sequencing data of nine studies generated from high-fat diet (HFD)-induced obese rodent models were processed with QIIME to obtain gut microbiota compositions. Biological functions were predicted and annotated with KEGG pathways with PICRUSt. No significant difference was observed for alpha diversity and Bacteroidetes-to-Firmicutes ratio between obese and lean rodents. Bacteroidia, Clostridia, Bacilli, and Erysipelotrichi were dominant classes, but gut microbiota compositions varied among studies. Meta-analysis of the nine microbiome data sets identified 15 differential taxa and 57 differential pathways between obese and lean rodents. In obese rodents, increased abundance was observed for Dorea, Oscillospira, and Ruminococcus, known for fermenting polysaccharide into short chain fatty acids (SCFAs). Decreased Turicibacter and increased Lactococcus are consistent with elevated inflammation in the obese status. Differential functional pathways of the gut microbiome in obese rodents included enriched pyruvate metabolism, butanoate metabolism, propanoate metabolism, pentose phosphate pathway, fatty acid biosynthesis, and glycerolipid metabolism pathways. These pathways converge in the function of carbohydrate metabolism, SCFA metabolism, and biosynthesis of lipid. HFD-induced obesity results in structural and functional dysbiosis of gut microbiota. The altered gut microbiome may contribute to obesity development by promoting insulin resistance and systemic inflammation.

Background: Periodontal pathogens have been isolated from precancerous and cancerous lesions and also shown to promote a procarcinogenic microenvironment. Few studies have examined periodontal disease as a risk factor for total cancer, and none have focused on older women. We examined whether periodontal disease is associated with incident cancer among postmenopausal women in the Women's Health Initiative Observational Study. Methods: Our prospective cohort study comprised 65,869 women, ages 54 to 86 years. Periodontal disease information was obtained via self-report questionnaires administered between 1999 and 2003, whereas ascertainment of cancer outcomes occurred through September 2013, with a maximum follow-up period of 15 years. Physician-adjudicated incident total cancers were the main outcomes and site-specific cancers were secondary outcomes. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. All analyses were conducted two-sided. Results: During a mean follow-up of 8.32 years, 7,149 cancers were identified. Periodontal disease history was associated with increased total cancer risk (multivariable-adjusted HR, 1.14; 95% CI, 1.08–1.20); findings were similar in analyses limited to 34,097 never-smokers (HR, 1.12; 95% CI, 1.04–1.22). Associations were observed for breast (HR, 1.13; 95% CI, 1.03–1.23), lung (HR, 1.31; 95% CI, 1.14–1.51), esophagus (HR, 3.28; 95% CI, 1.64–6.53), gallbladder (HR, 1.73; 95% CI, 1.01–2.95), and melanoma skin (HR, 1.23; 95% CI, 1.02–1.48) cancers. Stomach cancer was borderline (HR, 1.58; 95% CI, 0.94–2.67). Conclusions: Periodontal disease increases risk of total cancer among older women, irrespective of smoking, and certain anatomic sites appear to be vulnerable. Impact: Our findings support the need for further understanding of the effect of periodontal disease on cancer outcomes. Cancer Epidemiol Biomarkers Prev; 26(8); 1255–65. ©2017 AACR.

Through the use of optimal surveillance measures and standard case definitions, it is now possible to more accurately determine population-average risk profiles for severe (SP) and non-severe periodontitis (NSP) in adults (aged 30 years and older) in the United States.Data from the 2009 to 2012 National Health and Nutrition Examination Survey were used, which, for the first time, used the "gold standard" full-mouth periodontitis surveillance protocol to classify severity of periodontitis following suggested Centers for Disease Control/American Academy of Periodontology case definitions. Probabilities of periodontitis by: 1) sociodemographics, 2) behavioral factors, and 3) comorbid conditions were assessed using prevalence ratios (PRs) estimated by predicted marginal probability from multivariable generalized logistic regression models. Analyses were further stratified by sex for each classification of periodontitis.Likelihood of total periodontitis (TP) increased with age for overall and NSP relative to non-periodontitis. Compared with non-Hispanic whites, TP was more likely in Hispanics (adjusted [a]PR = 1.38; 95% confidence interval 95% CI: 1.26 to 1.52) and non-Hispanic blacks (aPR = 1.35; 95% CI: 1.22 to 1.50), whereas SP was most likely in non-Hispanic blacks (aPR = 1.82; 95% CI: 1.44 to 2.31). There was at least a 50% greater likelihood of TP in current smokers compared with non-smokers. In males, likelihood of TP in adults aged 65 years and older was greater (aPR = 2.07; 95% CI: 1.76 to 2.43) than adults aged 30 to 44 years. This probability was even greater in women (aPR = 3.15; 95% CI: 2.63 to 3.77). Likelihood of TP was higher in current smokers relative to non-smokers regardless of sex and periodontitis classification. TP was more likely in men with uncontrolled diabetes mellitus (DM) compared with adults without DM.Assessment of risk profiles for periodontitis in adults in the United States based on gold standard periodontal measures show important differences by severity of disease and sex. Cigarette smoking, specifically current smoking, remains an important modifiable risk for all levels of periodontitis severity. Higher likelihood of TP in older adults and in males with uncontrolled DM is noteworthy. These findings could improve identification of target populations for effective public health interventions to improve periodontal health of adults in the United States.

Extraoral translocation of oral bacteria may contribute to associations between periodontal disease and cancer. The associations among the presence of three orange-complex periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus), two red-complex periodontal pathogens (Porphyromonas gingivalis and Tannerella forsythia), and cancer risk were investigated.A total of 1,252 postmenopausal females enrolled in the Buffalo Osteoporosis and Periodontal Disease Study were followed prospectively. Baseline subgingival plaque samples were assessed for the presence of periodontal pathogens using indirect immunofluorescence. Incident cancer cases were adjudicated by staff physicians via review of medical records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of periodontal pathogens with total cancer and site-specific cancer risk in unadjusted and multivariable-adjusted models.Neither the presence of individual pathogens nor the presence of any red-complex pathogens was associated with total cancer or site-specific cancers. Borderline associations were seen among the presence of any orange-complex pathogens (F. nucleatum, P. intermedia, and C. rectus), total cancer risk (HR = 1.35, 95% CI = 1.00 to 1.84), and lung cancer risk (HR = 3.02, 95% CI = 0.98 to 9.29).No associations were found between the presence of individual subgingival pathogens and cancer risk. However, there were suggestions of borderline positive associations of the presence of any orange-complex pathogens with total cancer and lung cancer risk. The study is limited by the small number of cancer cases and the assessment of only five oral bacteria. Additional research is needed to understand the possible role of periodontal disease in carcinogenesis.

BACKGROUND: Multiple cross-sectional epidemiologic studies have suggested an association between periodontal disease and tooth loss and hypertension, but the temporality of these associations remains unclear. The objective of our study was to evaluate the association of baseline self-reported periodontal disease and edentulism with incident hypertension. METHODS: Study participants were 36,692 postmenopausal women in the Women’s Health Initiative-Observational Study who were followed annually from initial periodontal assessment (1998–2003) through 2015 (mean follow-up 8.3 years) for newly diagnosed treated hypertension. Cox proportional hazards regression with adjustment for potential confounders was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Edentulism was significantly associated with incident hypertension in crude (HR (95% CI) = 1.38 (1.28–1.49)) and adjusted (HR (95% CI) = 1.21 (1.11–1.30)) models. This association was stronger among those

PurposeThe Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) study is a prospective cohort study focused on the relationship between the microbiome and oral and systemic health outcomes in postmenopausal women. The cohort was established to examine how the oral microbiome is affected by (and how it affects) periodontal disease presence, severity and progression and to characterise the relationship between the microbiome, lifestyle habits and systemic disease outcomes.ParticipantsParticipants (n=1342) were postmenopausal women who were participating in the Women’s Health Initiative observational study at the Buffalo, New York clinical centre. There were 1026 participants at the 5-year follow-up visit and 518 at the 15-year visit.Findings to dateData collected include questionnaires, anthropometric measures, serum blood and saliva samples. At each clinic visit, participants completed a comprehensive oral examination to measure oral health and the oral microbiome. Preliminary findings have contributed to our understanding of risk factors for periodontal disease and the relationship between the oral microbiome and periodontal disease.Future plansThe novel microbiome data collected on a large sample of participants at three time points will be used to answer a variety of research questions focused on temporal changes in the microbiome and the relationship between the oral microbiome and oral and systemic disease outcomes. Little is currently known about the relationship between the oral microbiome and health outcomes in older adults; data from the OsteoPerio cohort will fill this gap. Microbiome samples are currently being analysed using next-generation sequencing technology with an anticipated completion date of late 2018.

Aging invokes physiological changes, such as immunosenescence and inflammation, that could increase host susceptibility to oral microbiome shifts that enable periodontitis progression in later life. At present, there is a dearth of studies specifically evaluating the oral microbiome and periodontitis in older adults. We used high-throughput untargeted sequencing methods and functional metagenomic analyses to assess and compare the subgingival biofilm of postmenopausal women (mean age 71 years) according to periodontitis status. Subgingival plaque samples were obtained from 15 postmenopausal women with no periodontitis, and from 15 women with severe periodontitis, determined by probing measures. The 16S rRNA gene (V1&ndash, V3 region) was sequenced on the 454 FLX platform. The PICRUSt technique was used to provide information on what the potential functional characteristics of microbiota might be in healthy, compared with diseased, periodontium. The subgingival microbiome associated with periodontitis showed clear differences to that associated with health. Of the 464 species identified, 22.8% had elevated abundance in disease, while only 6.3% had elevated abundance in health. Among the 12 most prevalent organisms in periodontitis, one-half have previously been recognized as periodontal pathogens by other investigators. The subgingival microbiome in periodontitis contained genes that could code for specific activities, including microbial mobility, synthesis of endotoxin, and proteolytic degradation. The healthy microbiome included genes that could code for sustaining microbial life, including encoding for transporters, glycolysis, gluconeogenesis, the Krebs cycle, and protein kinases. In the present study on postmenopausal women, aged 60 and older, the subgingival microbiome differed in composition and potential function between those with and without periodontitis. Studies of functional gene expression, such as transcriptomics, are needed to definitively identify the molecules carrying out functions associated with pathogenic subgingival complexes. This, in turn, could lead to identification of targets for enhanced management of periodontitis and, possibly, other diseases, in later life.

Periodontal disease (PD) is more common and severe in people with diabetes than the general population. The presence of severe PD is correlated with decreased survival, since it can potentially affect glycemic control and severity of complications in people with diabetes. We have reported that Medalists (people with T1DM of 50 years or longer duration) may have endogenous protective factors for the development of diabetic nephropathy (DN) and retinopathy (DR). This study assessed the prevalence of PD in the Medalist cohort and correlated it to the known risk factors of PD and diabetic complications. Severity of PD was defined in a subset (n=170) of Medalists with comparable characteristics of the whole cohort, according to the AAP criteria. The prevalence of severe PD was dramatically decreased in Medalists (13.5%) compared with other studies of people with diabetes of similar age, approximately 33%. Clinical parameters, such as male gender, chronological age, age at diagnosis, and total insulin dose were correlated positively with severity of PD (p=0.04, 0.01, 0.03, and 0.02, respectively), while duration of disease, hemoglobin A1c, BMI, and lipid profiles did not exhibit any correlation. Interestingly, detectible plasma C-peptide levels correlated inversely with severity of PD (p=0.04). Systemic inflammatory markers, such as plasma IL-6, clearly correlated positively with the severity of PD (p=0.01). Serum antibody titer against Porphyromonas gingivalis (Pg), a known pathogen of PD, trended with severity of PD (p=0.08). Amongst the various complications, only the prevalence of CVD correlated positively with severity of PD (p=0.02). These results suggest that Medalists are protected from severe PD even with hyperglycemia. The endogenous protective factors for PD could be similar to those for CVD, possibly related to endogenously produced insulin to neutralize the chronic inflammation caused by residual infection with Pg in the gingival tissues. Disclosure T. Shinjo: None. A. Ishikado: Employee; Self; Sunstar Inc.. Employee; Spouse/Partner; Sunstar Inc.. H. Hasturk: None. L.J. Tinsley: None. D.M. Pober: None. I. Wu: None. T.E. Van Dyke: None. R.J. Genco: None. G.L. King: Research Support; Self; Sanofi-Aventis.

This report presents weighted average estimates of the prevalence of periodontitis in the adult US population during the 6 years 2009-2014 and highlights key findings of a national periodontitis surveillance project.Estimates were derived for dentate adults 30 years or older from the civilian noninstitutionalized population whose periodontitis status was assessed by means of a full-mouth periodontal examination at 6 sites per tooth on all non-third molar teeth. Results are reported according to a standard format by applying the Centers for Disease Control and Prevention/American Academy of Periodontology periodontitis case definitions for surveillance, as well as various thresholds of clinical attachment loss and periodontal probing depth.An estimated 42% of dentate US adults 30 years or older had periodontitis, with 7.8% having severe periodontitis. Overall, 3.3% of all periodontally probed sites (9.1% of all teeth) had periodontal probing depth of 4 millimeters or greater, and 19.0% of sites (37.1% of teeth) had clinical attachment loss of 3 mm or greater. Severe periodontitis was most prevalent among adults 65 years or older, Mexican Americans, non-Hispanic blacks, and smokers.This nationally representative study shows that periodontitis is a highly prevalent oral disease among US adults.Dental practitioners should be aware of the high prevalence of periodontitis in US adults and may provide preventive care and counselling for periodontitis. General dentists who encounter patients with periodontitis may refer these patients to see a periodontist for specialty care.

Periodontal diseases are infections, and many forms of the disease are associated with specific pathogenic bacteria which colonize the subgingival area. At least two of these microorganisms, Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans, also invade the periodontal tissue and are virulent organisms. Initiation and progression of periodontal infections are clearly modified by local and systemic conditions called risk factors. The local factors include pre-existing disease as evidenced by deep probing depths and plaque retention areas associated with defective restorations. Systemic risk factors recently have been identified by large epidemiologic studies using multifactorial statistical analyses to correct for confounding or associated co-risk factors. Risk factors which we know today as important include diabetes mellitus, especially in individuals in whom metabolic control is poor, and cigarette smoking. These two risk factors markedly affect the initiation and progression of periodontitis, and attempts to manage these factors are now an important component of prevention and treatment of adult periodontitis. Systemic conditions associated with reduced neutrophil numbers or function are also important risk factors in children, juveniles, and young adults. Diseases in which neutrophil dysfunction occurs include the lazy leukocyte syndrome associated with localized juvenile periodontitis, cyclic neutropenia, and congenital neutropenia. Recent studies also point to several potentially important periodontal risk indicators. These include stress and coping behaviors, and osteopenia associated with estrogen deficiency. There are also background determinants associated with periodontal disease including gender (with males having more disease), age (with more disease seen in the elderly), and hereditary factors. The study of risk in periodontal disease is a rapidly emerging field and much is yet to be learned. However, there are at least two significant risk factors-smoking and diabetes-which demand attention in current management of periodontal disease. J Periodontol 1996;67:1041-1049.

The papers included here are taken from a symposium titled “Modern Periodontology – New Directions in the 21st Century.” This symposium was held to celebrate the 35th anniversary of the University at Buffalo Oral Biology Graduate Program, and the establishment of the Okayama University Graduate School of Medicine and Dentistry. The 2 institutions have shared many postdoctoral fellows and faculty studying periodontal diseases over the years. Hence, it was fitting to hold a joint symposium focusing on periodontal disease. The goal of the symposium was to provide a basis for 21st century periodontology, which we predict will be characterized by truly effective preventive and treatment strategies. These come from detailed knowledge of the etiology and pathogenesis of periodontal disease, and the papers here represent advances in our understanding of the pathogenic bacteria and their mechanisms of colonization and tissue destruction. Many of the papers deal with host-mediated tissue destruction that is triggered by bacteria, an important theme in the pathogenesis of periodontitis. The symposium opened with an introduction by Dr. Lawrence Tabak, director of the National Institute of Dental and Craniofacial Research. Dr. Tabak was one of the early students to receive his PhD from the Oral Biology program at the University at Buffalo. Dr. Tabak’s introduction is followed by a series of papers on host response to periodontal bacteria, followed by a series on tissue-destructive mechanisms of periodontal pathogens, with an emphasis on Porphyromonas gingivalis. The last 2 papers are fascinating in that they look at the ecology of Helicobacter bacteria in the oral cavity and the possible pathogenic cross-reactive activity between H. pylori and oral bacteria, and offer a hypothesis as to the contribution of oral infections to gastric ulcers. This symposium was held in Kanagawa, Japan and was supported by the Sunstar Company. All of the participants thank Sunstar for their support of the symposium, with special thanks to Mr. Hiroo Kaneda, president of Sunstar, for his generous support of the meeting and for his insights into the host response and systemic implications of periodontal disease that have spanned more than 2 decades.

This paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. It is intended to provide information for the dental profession and other interested parties. The purpose of this paper is to provide a general overview of oral reconstructive and corrective procedures used in periodontal therapy. It is not intended to be a comprehensive review of this subject.