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Frontiers in Endocrinology 2023Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of... (Review)
Review
Diabetes mellitus is a main risk factor for periodontitis, but until now, the underlying molecular mechanisms remain unclear. Diabetes can increase the pathogenicity of the periodontal microbiota and the inflammatory/host immune response of the periodontium. Hyperglycemia induces reactive oxygen species (ROS) production and enhances oxidative stress (OS), exacerbating periodontal tissue destruction. Furthermore, the alveolar bone resorption damage and the epigenetic changes in periodontal tissue induced by diabetes may also contribute to periodontitis. We will review the latest clinical data on the evidence of diabetes promoting the susceptibility of periodontitis from epidemiological, molecular mechanistic, and potential therapeutic targets and discuss the possible molecular mechanistic targets, focusing in particular on novel data on inflammatory/host immune response and OS. Understanding the intertwined pathogenesis of diabetes mellitus and periodontitis can explain the cross-interference between endocrine metabolic and inflammatory diseases better, provide a theoretical basis for new systemic holistic treatment, and promote interprofessional collaboration between endocrine physicians and dentists.
Topics: Humans; Diabetes Mellitus; Periodontitis; Hyperglycemia; Risk Factors; Bone Resorption
PubMed: 37664859
DOI: 10.3389/fendo.2023.1192625 -
Journal of Periodontal Research Dec 2023Periodontitis, a chronic infectious disease, primarily arises from infections and the invasion of periodontal pathogens. This condition is typified by alveolar bone loss... (Review)
Review
Periodontitis, a chronic infectious disease, primarily arises from infections and the invasion of periodontal pathogens. This condition is typified by alveolar bone loss resulting from host immune responses and inflammatory reactions. Periodontal pathogens trigger aberrant inflammatory reactions within periodontal tissues, thereby exacerbating the progression of periodontitis. Simultaneously, these pathogens and metabolites stimulate osteoclast differentiation, which leads to alveolar bone resorption. Moreover, a range of systemic diseases, including diabetes, postmenopausal osteoporosis, obesity and inflammatory bowel disease, can contribute to the development and progression of periodontitis. Many studies have underscored the pivotal role of gut microbiota in bone health through the gut-alveolar bone axis. The circulation may facilitate the transfer of gut pathogens or metabolites to distant alveolar bone, which in turn regulates bone homeostasis. Additionally, gut pathogens can elicit gut immune responses and direct immune cells to remote organs, potentially exacerbating periodontitis. This review summarizes the influence of oral microbiota on the development of periodontitis as well as the association between gut microbiota and periodontitis. By uncovering potential mechanisms of the gut-bone axis, this analysis provides novel insights for the targeted treatment of pathogenic bacteria in periodontitis.
Topics: Humans; Alveolar Bone Loss; Gastrointestinal Microbiome; Periodontitis; Inflammation; Periodontium
PubMed: 37712722
DOI: 10.1111/jre.13168 -
Journal of Basic Microbiology Oct 2023Alzheimer's disease causes memory loss and dementia in older adults through a neurodegenerative mechanism. Despite the pathophysiological clarification of this cognitive... (Review)
Review
Alzheimer's disease causes memory loss and dementia in older adults through a neurodegenerative mechanism. Despite the pathophysiological clarification of this cognitive disorder, novel molecular and cellular pathways should be identified to determine its exact mechanism. Alzheimer's disease (AD) is pathologically characterized by senile plaques comprising beta-amyloid and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau as a microtubule-associated protein with a key role in the pathogenesis of AD. Periodontitis through inflammatory pathways is a risk factor for deteriorating cognitive impairment in AD patients. Poor oral hygiene coupled with immunocompromised status in older adults causes periodontal diseases and chronic inflammations through an oral bacterial imbalance. Toxic bacterial products, including bacteria themselves, can reach the central nervous system through the bloodstream and evoke inflammatory responses. The present review was conducted to investigate relationships between AD and periodontitis-involved bacteria as a risk factor.
Topics: Humans; Aged; Alzheimer Disease; Amyloid beta-Peptides; Neurofibrillary Tangles; Periodontitis; Bacteria
PubMed: 37311215
DOI: 10.1002/jobm.202300250 -
Journal of Dental Research Nov 2023Dendritic cells (DCs) can mediate inflammation-related bone resorption that is crucial in the development of periodontitis. Butyrate is a critical by-product of microbes...
Dendritic cells (DCs) can mediate inflammation-related bone resorption that is crucial in the development of periodontitis. Butyrate is a critical by-product of microbes with antibacterial and anti-inflammatory properties. Here, we found that butyrate inhibited the activation of lipopolysaccharide (LPS)-induced DCs and generation of inflammatory cytokines by DCs. Moreover, butyrate regulated glycolysis in LPS-induced DCs via the G-protein-coupled receptor/hypoxia-inducible factor-1α pathway. In addition, butyrate inhibited the maturation of CD11cMHC-II DCs in vivo, suppressing local inflammatory infiltration and ultimately alleviating bone resorption in a periodontitis model. Our results imply that butyrate suppresses the activation of LPS-induced DCs by modulating their metabolism, highlighting its potential as a therapeutic agent for inflammatory diseases.
Topics: Humans; Butyrates; Lipopolysaccharides; Dendritic Cells; Cytokines; Periodontitis; Bone Resorption
PubMed: 37775917
DOI: 10.1177/00220345231187824 -
Journal of Dental Research Apr 2024Mounting evidence indicates that periodontitis-related oral bacteria may contribute to gut microbial dysbiosis. This clinical study aimed to explore the oral-gut...
Mounting evidence indicates that periodontitis-related oral bacteria may contribute to gut microbial dysbiosis. This clinical study aimed to explore the oral-gut microbial signatures associated with periodontitis and to longitudinally evaluate the effect of periodontal treatment on the oral and gut microbial composition. Stool and saliva samples from generalized stage III/IV periodontitis patients ( = 47) were collected and analyzed by 16S ribosomal RNA gene amplicon sequencing, before and 3 mo after steps I to II of periodontal therapy. Periodontally healthy matched subjects ( = 47) were used as controls. Principal component analysis was carried out to identify oral-gut microbial profiles between periodontitis patients at baseline and healthy subjects; periodontitis samples were longitudinally compared before and after treatment. β-Diversity of gut microbial profiles of periodontitis patients before treatment significantly differed from healthy controls ( < 0.001). Periodontal therapy was associated with a significant change in gut microbiota ( < 0.001), with post-treatment microbial profiles similar to healthy volunteers. A higher abundance of , , , and was noted in fecal samples of periodontitis patients at baseline compared to healthy controls. In contrast, was the only genus more abundant in the latter. Additionally, periodontal therapy led to a parallel reduction in the salivary carriage of periodontal pathobionts, as well as gut , , , , and , to levels similar to healthy controls. Collectively, discriminating oral-gut microbial signatures of periodontitis were found. Periodontal treatment both mitigated oral dysbiosis and altered gut microbial composition, signifying potential broader implications for gastrointestinal health and disease.
Topics: Humans; Gastrointestinal Microbiome; Dysbiosis; RNA, Ribosomal, 16S; Periodontitis; Microbiota
PubMed: 38362600
DOI: 10.1177/00220345231222800 -
Journal of Periodontal Research Aug 2023Periodontitis is a chronic inflammatory disease involving soft and hard tissue destruction in the periodontal region. Cannabidiol (CBD) is a natural compound isolated...
BACKGROUND AND OBJECTIVE
Periodontitis is a chronic inflammatory disease involving soft and hard tissue destruction in the periodontal region. Cannabidiol (CBD) is a natural compound isolated from cannabis, which has the effect of inhibiting inflammation. However, the role of CBD in periodontitis remains unclear. The aim of this study was to investigate the anti-inflammatory effects and osteoprotective actions of CBD in periodontitis and its molecular mechanisms.
MATERIALS AND METHODS
After establishing the rat periodontitis model by ligatures, the specimens were processed for morphometric analysis by Micro-CT. The gingival tissues were collected, and the levels of TNF-α, IL-1β, and TLR4 were measured by enzyme-linked immunosorbent assay. LPS was used to induce the inflammatory response of human periodontal ligament cells (hPDLCs) in vitro. QPCR and western blot were carried out to detect the expression of related inflammatory cytokines and signaling pathways.
RESULTS
Cannabidiol significantly inhibits bone loss in experimental rat periodontitis models. CBD downregulated the pro-inflammatory mediator TNF-α, related to the decrease of TLR4 protein expression. Overexpression of TNF-α and TLR4 caused by LPS in hPDLCs. CBD inactivated the TLR4/NF-κB signaling pathway by inhibiting TLR-4 expression and p65 NF-κB phosphorylation. CBD can be considered as a therapeutic agent for periodontitis.
CONCLUSION
Our study demonstrated that CBD attenuates ligature-induced periodontitis in rats and LPS-induced inflammation in hPDLCs by inhibiting TLR4/NF-κB pathway activation. It indicates that topical CBD application is effective in treating periodontitis.
Topics: Humans; Rats; Animals; NF-kappa B; Cannabidiol; Tumor Necrosis Factor-alpha; Lipopolysaccharides; Toll-Like Receptor 4; Inflammation; Periodontitis
PubMed: 37143211
DOI: 10.1111/jre.13118 -
BMC Oral Health Nov 2023Studies indicate that treating periodontitis may benefit glycemic control among people with diabetes. It is unclear whether oral self-care such as flossing may reduce...
BACKGROUND
Studies indicate that treating periodontitis may benefit glycemic control among people with diabetes. It is unclear whether oral self-care such as flossing may reduce risk for periodontitis and improve glycemic control among people with diabetes. The purpose of this study was to examine associations between oral care, specifically, flossing and preventive dental care, with periodontitis and glycemic control, among US dentate adults with diabetes.
METHODS
We analyzed data from the National Health and Nutrition Examination Survey 2011-2014 for 892 participants aged 30 years and older with diabetes who completed the periodontal examination and lab test for hemoglobin A1c (HbA1c). Sampling weights were applied. Multivariable logistic regression and multivariable linear modeling were performed to examine the associations of flossing and preventive dental services on periodontal health and HbA1c levels, respectively, controlling for sociodemographic characteristics, health behaviors, and other risk factors.
RESULTS
Among U.S. dentate adults with diabetes, 52.1% of flossers and 72.1% of non-flossers had periodontitis (p < 0.001). Flossers were 39% less likely to have periodontitis (Adj. OR 0.61, 95% CI 0.43-0.88) compared to non-flossers. Flossers had an average HbA1c reading 0.30% (95% CI 0.02%-0.58%) lower than non-flossers, adjusted for covariates (p = 0.037). Preventive dental visits were associated with reduced risk for periodontitis (Adj. OR 0.54, 95%CI, 0.38-0.75) but not glycemic control.
CONCLUSION
Flossing was associated with periodontal health and glycemic control among US adults with diabetes. Although further research is needed, the findings support that oral self-care may be particularly beneficial for adults with diabetes.
Topics: Adult; Humans; Glycated Hemoglobin; Glycemic Control; Nutrition Surveys; Diabetes Mellitus; Periodontitis; Diabetes Mellitus, Type 2
PubMed: 37990177
DOI: 10.1186/s12903-023-03580-0 -
Frontiers in Public Health 2023Type 2 diabetes and its associated cardiovascular risk is an escalating epidemic that represents a significant public health burden due to increased morbidity and... (Review)
Review
Type 2 diabetes and its associated cardiovascular risk is an escalating epidemic that represents a significant public health burden due to increased morbidity and mortality, disproportionately affecting disadvantaged communities. Poor glycaemic control exacerbates this burden by increasing retinal, renal, and cardiac damage and raising healthcare costs. This predicament underscores the urgent need for research into cost-effective approaches to preventing diabetes complications. An important but often overlooked strategy to improve metabolic control in diabetic patients is the treatment of periodontitis. Our aim is to assess whether the inclusion of periodontitis treatment in diabetes management strategies can effectively improve metabolic control, and to advocate for its inclusion from an equity perspective. We conducted a comprehensive review of the literature from 2000 to 2023. We analyzed the pathophysiological links between periodontitis, diabetes, and atherosclerotic cardiovascular disease, all of which have inflammation as a central component. We also examined the inequalities in health care spending in this context. Our findings suggest that incorporating routine screening and treatment of periodontitis into national health programs, with coordinated efforts between physicians and dentists, is a cost-effective measure to improve metabolic control, reduce complications and improve the overall quality of life of people with diabetes.
Topics: Humans; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Quality of Life; Periodontitis; Epidemics
PubMed: 38192555
DOI: 10.3389/fpubh.2023.1270557 -
BMC Medicine Nov 2023Recent studies have highlighted the role of low-grade systemic inflammation in linking periodontitis to cardiovascular disease (CVD) outcomes, but many aspects remain...
BACKGROUND
Recent studies have highlighted the role of low-grade systemic inflammation in linking periodontitis to cardiovascular disease (CVD) outcomes, but many aspects remain unclear. This study examines the independent and reciprocal associations of periodontitis and low-grade systemic inflammation with all-cause and CVD mortality in a large-scale cohort.
METHODS
A total of 3047 participants from the prospective, population-based Study of Health in Pomerania (SHIP-START) were followed for a period of 13.0 ± 2.4 years. For the association between various inflammation/periodontitis measures and mortality, hazard ratios (HRs) were obtained from covariate-adjusted Cox proportional hazards models. Interactions were analysed in joint models: on the multiplicative scale, HRs were reported and on the additive scale, relative excess risks due to interaction (RERI) were calculated. Subject and variable-specific interval records were used to account for time-varying exposures and covariates.
RESULTS
During the observation period, 380 (12.5%) individuals died from CVD (n = 125) or other causes (n = 255). All markers of periodontitis and inflammation showed apparent associations with all-cause mortality (HRs per SD-increase: mean PPD: 1.068 (95% confidence interval (CI): 0.988-1.155), mean CAL: 1.205 (95% CI: 1.097-1.323), missing teeth: 1.180 (95% CI: 1.065-1.307), periodontitis score: 1.394 (95% CI: 1.202-1.616), leukocytes: 1.264 (95% CI: 1.163-1.374), fibrinogen: 1.120 (95% CI: 1.030-1.218), CRP: 1.231 (95% CI: 1.109-1.366), inflammation score: 1.358 (95% CI: 1.210-1.523)). For CVD mortality, all PPD related variables showed significant associations. Interaction modelling revealed some variation with respect to mortality type and exposure combinations. On the additive scale, RERIs for periodontitis score and inflammation score implied 18.9% and 27.8% excess mortality risk for all-cause and CVD mortality, respectively. On the multiplicative scale, the HRs for interaction were marginal.
CONCLUSIONS
Both periodontitis and inflammation were significantly associated with all-cause mortality and CVD mortality. On the additive scale, a substantial excess risk was observed due to the interaction of periodontitis and inflammation, suggesting that the greatest treatment benefit may be achieved in patients with both periodontitis and high systemic inflammation. As periodontal therapy has been reported to also reduce systemic inflammation, the possibility of a reduction in CVD mortality risk by anti-inflammatory treatments, including periodontal interventions, seems worthy of further investigation.
Topics: Humans; Prospective Studies; Cardiovascular Diseases; Periodontitis; Inflammation; Risk Factors
PubMed: 37953258
DOI: 10.1186/s12916-023-03139-4 -
Journal of Periodontal Research Apr 2024As a chronic inflammatory disease, periodontitis threatens oral health and is a risk factor for Alzheimer's disease (AD). There is growing evidence that these two...
BACKGROUND AND OBJECTIVE
As a chronic inflammatory disease, periodontitis threatens oral health and is a risk factor for Alzheimer's disease (AD). There is growing evidence that these two diseases are closely related. However, current research is still incomplete in understanding the common genes and common mechanisms between periodontitis and AD. In this study, we aimed to identify common genes in periodontitis and AD and analyze the relationship between crucial genes and immune cells to provide new therapeutic targets for clinical treatment.
MATERIALS AND METHODS
We evaluated differentially expressed genes (DEGs) specific to periodontitis and AD. Co-expressed genes were identified by obtaining gene expression profile data from the Gene Expression Omnibus (GEO) database. Using the STRING database, protein-protein interaction (PPI) networks were constructed, and essential genes were identified. We also used four algorithms to identify critical genes and constructed regulatory networks. The association of crucial genes with immune cells and potential therapeutic effects was also assessed.
RESULTS
PDGFRB, VCAN, TIMP1, CHL1, EFEMP2, and IGFBP5 were obtained as crucial common genes. Immune infiltration analysis showed that Natural killer cells and Myeloid-derived suppressor cells were significantly differentially expressed in patients with PD and AD compared with the normal group. FOXC1 and GATA2 are important TFs for PD and AD. MiR-23a, miR-23b, miR-23a, and miR-23b were associated with AD and PD. Finally, the hub genes retrieved from the DSigDB database indicate multiple drug molecule and drug-target interactions.
CONCLUSION
This study reveals commonalities in common hub genes and immune infiltration between periodontitis and AD, and the analysis of six hub genes and immune cells may provide new insights into potential therapeutic directions for the pathogenesis of periodontitis complicated by AD.
Topics: Humans; Alzheimer Disease; Periodontitis; Computational Biology; Databases, Factual; MicroRNAs; Gene Expression Profiling
PubMed: 38189472
DOI: 10.1111/jre.13220