• Alveolar bone loss
• Bone marrow stem cells
• Cellular senescence
• Chromatin accessibility
• Pamidronate

• Animals
• Activating Transcription Factor 2/metabolism
• Cellular Senescence/drug effects
• Mice
• Pamidronate/pharmacology
• Jaw/metabolism
• Bone Marrow Cells/metabolism
• Bone Marrow Cells/cytology
• Mice, Inbred C57BL
• Mesenchymal Stem Cells/metabolism
• Mesenchymal Stem Cells/drug effects
• Mesenchymal Stem Cells/cytology

• chronic periodontitis periodontal diseases
• non‐alcoholic fatty liver disease
• retrospective studies

• Community periodontal index
• Oral health
• Periodontal disease
• Remaining teeth
• Sex characteristics
• Type 2 diabetes mellitus

• GWAS
• Mendelian randomization
• NAFLD‐related diseases
• epidemiological studies
• periodontitis

• Mendelian Randomization Analysis
• Humans
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/epidemiology
• Periodontitis/genetics
• Genome-Wide Association Study
• Liver Cirrhosis/genetics
• Polymorphism, Single Nucleotide
• Genetic Markers

• ZC20134 The Science and Technology Project of Tianjin Health Commission

• 3x‐Tg mice
• dementia
• dementia‐associated Aβ42 and p‐tau (T181)
• osteoclastogenic RANKL
• periodontitis
• sex

• Animals
• Female
• Alveolar Bone Loss/pathology
• Alveolar Bone Loss/diagnostic imaging
• Alveolar Bone Loss/metabolism
• Male
• Mice
• Dementia/etiology
• Humans
• Mice, Transgenic
• Aged
• RANK Ligand/analysis
• RANK Ligand/metabolism
• Sex Factors
• Periodontitis/complications
• Periodontitis/pathology
• Disease Models, Animal
• X-Ray Microtomography
• Osteoclasts/pathology
• Amyloid beta-Peptides/metabolism
• Gingival Crevicular Fluid/chemistry
• Peptide Fragments/analysis
• Risk Factors

• NIAMS NIH HHS
• NIDCR NIH HHS
• NIA NIH HHS
• NIAMS NIH HHS
• NIDCR NIH HHS
• NIA NIH HHS

• Gut bacteria
• Non-alcoholic fatty liver disease
• Non-alcoholic steatohepatitis
• Oral bacteria
• Periodontitis

• obesity
• overweight
• periodontal disease
• periodontitis
• review

• Humans
• Periodontal Diseases/complications
• Periodontal Diseases/epidemiology
• Obesity/complications

• gender
• gender differences
• oral diagnosis
• sex differences
• sex dimorphism
• sex predilection

• Animals
• Humans
• Male
• Female
• Periodontal Diseases/prevention & control
• Oral Health
• Dental Caries/prevention & control
• Disease Susceptibility
• Sex Characteristics

• Cardiovascular diseases
• Fatty liver
• Non-alcoholic fatty liver disease
• Patient care team

• Humans
• Non-alcoholic Fatty Liver Disease/therapy
• Non-alcoholic Fatty Liver Disease/complications
• Carcinoma, Hepatocellular/complications
• Liver Neoplasms/complications

• Non-alcoholic fatty liver disease
• Oral health
• Periodontal disease

• Humans
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/complications
• Cross-Sectional Studies
• Retrospective Studies
• Prospective Studies
• Periodontal Diseases/complications
• Periodontal Diseases/epidemiology

• acute rejection
• infection foci
• liver transplantation
• oral disease
• oral health

• P. gingivalis
• dysbiosis
• multiple parallel hits
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis
• periodontitis
• treatment

• Humans
• Non-alcoholic Fatty Liver Disease/etiology
• Liver/pathology
• Risk Factors
• Obesity/complications
• Periodontal Diseases/complications

• Dysbiosis
• Metabolic syndrome
• Microbiota
• Nonalcoholic fatty liver disease
• Periodontal disease
• Probiotics

• Animals
• Dysbiosis/microbiology
• Fibrosis
• Inflammation/pathology
• Liver/pathology
• Metabolic Syndrome/complications
• Microbiota
• Non-alcoholic Fatty Liver Disease/pathology
• Periodontitis/therapy
• Periodontitis/complications
• Periodontitis/metabolism
• Intestines

• R01 DE025225 NIDCR NIH HHS

• meta-analysis
• obesity
• observational study
• periodontitis
• systematic review

• Humans
• Adolescent
• Young Adult
• Adult
• Periodontitis/complications
• Periodontitis/epidemiology
• Obesity/complications
• Obesity/epidemiology
• Odds Ratio
• Body Weight
• Brazil

• National Research Foundation of Korea

• Insulin resistance
• Non-alcoholic fatty liver disease
• chronic periodontitis
• inflammatory response

• alanine aminotransferase
• leucocyte counts
• metabolic syndrome
• racial differences
• stage II/III localized periodontitis

Periodontal disease, a chronic inflammatory disease of the periodontal tissues, is not only a major cause of tooth loss, but it is also known to exacerbate/be associated with various metabolic disorders, such as obesity, diabetes, dyslipidemia, and cardiovascular disease. Recently, growing evidence has suggested that periodontal disease has adverse effects on the pathophysiology of liver disease. In particular, nonalcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome, has been associated with periodontal disease. Nonalcoholic fatty liver disease is characterized by hepatic fat deposition in the absence of a habitual drinking history, viral infections, or autoimmune diseases. A subset of nonalcoholic fatty liver diseases can develop into more severe and progressive forms, namely nonalcoholic steatohepatitis. The latter can lead to cirrhosis and hepatocellular carcinoma, which are end‐stage liver diseases. Extensive research has provided plausible mechanisms to explain how periodontal disease can negatively affect nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, namely via hematogenous or enteral routes. During periodontitis, the liver is under constant exposure to various pathogenic factors that diffuse systemically from the oral cavity, such as bacteria and their by‐products, inflammatory cytokines, and reactive oxygen species, and these can be involved in disease promotion of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, gut microbiome dysbiosis induced by enteral translocation of periodontopathic bacteria may impair gut wall barrier function and promote the transfer of hepatotoxins and enterobacteria to the liver through the enterohepatic circulation. Moreover, in a population with metabolic syndrome, the interaction between periodontitis and systemic conditions related to insulin resistance further strengthens the association with nonalcoholic fatty liver disease. However, most of the pathologic links between periodontitis and nonalcoholic fatty liver disease in humans are provided by epidemiologic observational studies, with the causal relationship not yet being established. Several systematic and meta‐analysis studies also show conflicting results. In addition, the effect of periodontal treatment on nonalcoholic fatty liver disease has hardly been studied. Despite these limitations, the global burden of periodontal disease combined with the recent nonalcoholic fatty liver disease epidemic has important clinical and public health implications. Emerging evidence suggests an association between periodontal disease and liver diseases, and thus we propose the term periodontal disease–related nonalcoholic fatty liver disease or periodontal disease–related nonalcoholic steatohepatitis. Continued efforts in this area will pave the way for new diagnostic and therapeutic approaches based on a periodontologic viewpoint to address this life‐threatening liver disease.

• NAFLD
• NASH
• gut microbial dysbiosis
• metabolic syndrome
• obesity
• periodontal disease
• periodontopathic bacteria
• systemic inflammation

• NAFLD
• immunological response
• inflammation
• microbiome
• periodontal disease

• Animals
• Humans
• Immunity, Innate
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/etiology
• Periodontal Diseases/complications
• Periodontal Diseases/epidemiology
• T-Lymphocytes/physiology

• 20H03863 Japan Society for the Promotion of Science

• Bleeding on probing
• case control
• nonalcoholic fatty liver disease
• oral health
• periodontal disease
• systemic health
• tumor necrosis factor

We report the first protocol for a multicenter, randomized comparison study to compare the efficacies of periodontal scaling and root-planing treatment against that of tooth-brushing treatment for nonalcoholic fatty liver disease (NAFLD) (PERION: PERIOdontal treatment for NAFLD). Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, which can progress to cirrhosis and hepatocellular carcinoma. Increased endotoxemia is associated with the progression of NAFLD. Periodontal bacteria possess endotoxins; Porphyromonas gingivalis is well-known as a major pathogenic bacterium in periodontitis, and serum antibody levels for P. gingivalis are high in patients with periodontitis. Several reports have indicated that P. gingivalis is related to NAFLD. This study aims to investigate the effect of periodontal treatment for liver damage, P. gingivalis infection, and endotoxemia on patients with NAFLD.

We will include adult patients (20–85 years old) with NAFLD, alanine aminotransferase (ALT) ≥ 40 IU/L, and equivalent steatosis grade ≥ 1 (target sample size, n = 40 patients; planned number of patients with outcome data, n = 32). Participants will be randomly assigned to one of two groups: a scaling and root-planing group or tooth-brushing as the usual group. The primary outcome will be the change in ALT levels from baseline to 12 weeks; the key secondary outcome will be the change in the serum immunoglobulin G (IgG) antibody titer for P. gingivalis at 12 weeks.

This study should determine whether periodontal treatment decreases liver damage, P. gingivalis infection, and endotoxemia in patients with NAFLD.

University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000022079.

• Alanine aminotransferase
• Immunoglobulin G
• Lipopolysaccharides
• NAFLD
• Periodontal treatment
• Porphyromonas gingivalis

• Obesity
• adolescent
• periodontal disease
• young adult

Periodontal disease is closely related to lifestyle-related diseases and obesity. It is widely known that moderate exercise habits lead to improvement in lifestyle-related diseases and obesity. However, little research has been undertaken into how exercise habits affect periodontal disease. The purpose of this study was to examine the effect of exercise habits on periodontal diseases and metabolic pathology.

We conducted a prospective intervention research for 12 weeks. The subjects were 71 obese men who participated in an exercise and/or dietary intervention program. Fifty subjects were assigned to exercise interventions (exercise intervention group) and 21 subjects were assigned to dietary interventions (dietary intervention group). This research was conducted before and after each intervention program.

In the exercise intervention group, the number of teeth with a probing pocket depth (PPD) ≥4 mm significantly decreased from 14.4% to 5.6% (P<0.001), and the number of teeth with bleeding on probing (BOP) significantly decreased from 39.8% to 14.4% (P<0.001). The copy counts of Tannerella forsythia and Treponema denticola decreased significantly (P=0.001). A positive correlation was found between the change in the copy count of T. denticola and the number of teeth with PPD ≥4 mm (P=0.003) and the number of teeth with BOP (P=0.010). A positive correlation was also found between the change in the copy count of T. denticola and body weight (P=0.008), low-density lipoprotein cholesterol (P=0.049), and fasting insulin (P=0.041). However, in the dietary intervention group the copy count of T. denticola decreased significantly (P=0.007) and there was no correlation between the number of periodontal disease-causing bacteria and PPD and BOP.

Our results are the first to show that exercise might contribute to improvements in periodontal disease.

• bacteria
• intervention studies
• lifestyle
• metabolic syndrome
• obesity
• periodontal disease
• periodontal status

• disease
• free radicals
• inflammation
• oral
• oxidative stress
• pathways

Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue.

• bacteria
• cirrhosis
• hepatocellular carcinoma
• liver transplantation
• non-alcoholic fatty liver disease
• periodontitis

Objective. Alanine Aminotransferase is an enzyme associated with not only liver diseases, liver conditions, and metabolic syndrome, but also inflammation. Periodontitis is associated with increased cytokines and other markers of inflammation. The purpose of this study is to determine if an independent association between Alanine Aminotransferase and periodontitis exists. Methods. Data from the 2009-2010 and 2011-2012 National Health and Nutrition Surveys (NHANES) were combined. Data concerning periodontitis and Alanine Aminotransferase were extracted and analyzed with Rao Scott Chi-square and logistic regressions. Serum Alanine Aminotransferase was dichotomized at 40 units/liter, and periodontitis was dichotomized to the presence or absence of periodontitis. Results. In bivariate Chi-square analyses, periodontitis and Alanine Aminotransferase were associated (p = 0.0360) and remained significant in unadjusted logistic regression (OR = 1.30 [95% CI: 1.02, 1.65]). However, when other known risk factors of periodontitis were included in the analyses, the relationship attenuated and failed to reach significance (adjusted OR = 1.17 [95% CI: 0.85, 1.60]). Conclusion. Our study adds to the literature a positive but attenuated association of serum Alanine Aminotransferase with periodontitis which failed to reach significance when other known, strong risk factors of periodontitis were included in the analysis.

Periodontitis is the commonest oral disease affecting population worldwide. This disease is notorious for the devastation of tooth supporting structures, ensuing in the loss of dentition. The etiology for this disease is bacterial biofilm, which accumulates on the teeth as dental plaque. In addition to the biofilm microorganisms, other factors such as environmental, systemic and genetic are also responsible in progression of periodontitis. Diabetes mellitus (DM) is metabolic disorder which has an impact on the global health. DM plays a crucial role in the pathogenesis of periodontitis. Periodontitis is declared as the “sixth” major complication of DM. Evidence based literature has depicted an enhanced incidence and severity of periodontitis in subjects with DM. A “two way” relationship has been purported between periodontitis and DM. Mutual management of both conditions is necessary. Periodontal therapy (PT) may assist to diminish the progression of DM and improve glycemic control. Various advanced technological facilities may be utilized for the purpose of patient education and disease management. The present paper clarifies the etio-pathogenesis of periodontitis, establishing it as a complication of DM and elaborating the various mechanisms involved in the pathogenesis. The role of PT in amelioration of DM and application of digital communication will be discussed. Overall, it is judicious to create an increased patient cognizance of the periodontitis-DM relationship. Conjunctive efforts must be undertaken by the medical and oral health care professionals for the management of periodontitis affected DM patients.

• Cost-effectiveness
• Advanced glycation end products
• Complications
• Glycated hemoglobin
• Inflammation
• Mobile health
• Periodontitis
• Periodontal therapy
• Scaling and root planing
• Type 2 diabetes mellitus

This population-based study determined the salivary microbiota composition of 2,343 adult residents of Hisayama town, Japan, using 16S rRNA gene next-generation high-throughput sequencing. Of 550 identified species-level operational taxonomic units (OTUs), 72 were common, in ≥75% of all individuals, as well as in ≥75% of the individuals in the lowest quintile of phylogenetic diversity (PD). These “core” OTUs constituted 90.9 ± 6.1% of each microbiome. The relative abundance profiles of 22 of the core OTUs with mean relative abundances ≥1% were stratified into community type I and community type II by partitioning around medoids clustering. Multiple regression analysis revealed that a lower PD was associated with better conditions for oral health, including a lower plaque index, absence of decayed teeth, less gingival bleeding, shallower periodontal pockets and not smoking, and was also associated with tooth loss. By contrast, multiple Poisson regression analysis demonstrated that community type II, as characterized by a higher ratio of the nine dominant core OTUs, including Neisseria flavescens, was implicated in younger age, lower body mass index, fewer teeth with caries experience, and not smoking. Our large-scale data analyses reveal variation in the salivary microbiome among Japanese adults and oral health-related conditions associated with the salivary microbiome.

• behavioral science
• cross-sectional studies
• psychological symptoms
• structural equation modeling
• university students

• Adult
• Anxiety/psychology
• Attitude to Health
• Dental Anxiety/psychology
• Dental Care/psychology
• Dental Devices, Home Care
• Depression/psychology
• Female
• Health Behavior
• Humans
• Male
• Models, Psychological
• Oral Health
• Sex Factors
• Students/psychology
• Surveys and Questionnaires
• Toothbrushing/psychology
• Universities
• Young Adult

• Enzyme-linked immunosorbent assay
• Toll-like receptor 4
• interleukin-18
• periodontitis
• transaminases
• uric acid

• body mass index
• cohort studies
• obesity
• oral health behaviours
• periodontal disease
• university students

Although triglyceride accumulation in the liver causes non-alcoholic fatty liver disease (NAFLD), hypercholesterolemia is also a main cause of NAFLD as well as atherosclerosis. However, NAFLD and atherosclerosis have not been investigated simultaneously in animal models fed a high-cholesterol diet. Moreover, it is unclear whether systemic inflammation can exacerbate both pathologies in the same model. Accordingly, this study investigated the effect of additional systemic inflammation on NAFLD and atherosclerosis induced by cholesterol overload in wild animals. New Zealand white rabbits were divided into 4 groups: groups I (control) and II received normal chow, and groups III and IV received a 1% cholesterol diet. To induce inflammation via toll-like receptor (TLR)-4 signaling, groups II and IV received subcutaneous injections of 0.5 mL of 1% carrageenan every 3 weeks. After 3 months, total cholesterol markedly increased in groups III and IV, and the serum expressions of systemic inflammatory markers were elevated in the groups II–IV. Early NAFLD lesions (e.g., mild fatty changes in the liver with sporadic fibrosis) and atherosclerosis (e.g., intimal hyperplasia composed of foam cells) were observed in both the liver and aorta specimens from group III, and advanced lesions were observed in group IV. The expressions of inflammatory cellular receptors, TLR-2 and TLR-4, in the aorta gradually increased from group I to IV but were similar in the liver in groups II–IV. Cholesteryl ester (CE) levels were higher in group IV than in group III, although the difference was not significant. CE levels in the aorta were similar between groups III and IV. Systemic inflammation can simultaneously exacerbate existing early lesions due to cholesterol overload in both the liver and aorta of rabbits. However, the cellular response of inflammatory receptors and expression of cholesterol metabolites differ between these organs.

Aims: Periodontal disease and metabolic syndrome (MS) are more prevalent in males than in females. However, whether there is a gender difference in the association between these health conditions has not yet been investigated. This study examined the gender difference in this association, considering the definition of periodontal disease.

Materials and Methods: We recruited 1040 males and 1330 females, aged ≥40 years, with at least ten teeth from subjects of the 2007 Hisayama health examination. We performed a logistic regression analysis with various definitions of periodontal disease the dependent variable and MS as the independent variable. Following the analysis, the data were reanalysed with the structural equations model.

Results: The logistic regression analysis suggested a stronger association between periodontal disease and MS in females than that in males when periodontal disease was more severely defined. When we constructed the structural equations model in each gender, the model showed a good fit to the data of females, suggesting the association between periodontal disease and MS in females, but not in males.

Conclusions: Gender differences seem to exist in the association between periodontal disease and MS; MS might show a stronger association with periodontal disease in females than in males.

Furuta M, Shimazaki Y, Takeshita T, Shibata Y, Akifusa S, Eshima N, Kiyohara Y, Ninomiya T, Hirakawa Y, Mukai N, Nagata M, Yamashita Y. Gender differences in the association between metabolic syndrome and periodontal disease: the Hisayama Study. J Clin Periodontol 2013; 40: 743–752. doi: 10.1111/jcpe.12119.

• gender difference
• metabolic syndrome
• periodontal disease
• structural equation model