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Lipopolysaccharide is a virulence factor of gram-negative bacteria with a crucial importance to the bacterial surface integrity. From the host's perspective, lipopolysaccharide plays a role in both local and systemic inflammation, activates both innate and adaptive immunity, and can trigger inflammation either directly (as a microbe-associated molecular pattern) or indirectly (by inducing the generation of nonmicrobial, danger-associated molecular patterns). Translocation of lipopolysaccharide into the circulation causes endotoxemia, which is typically measured as the biological activity of lipopolysaccharide to induce coagulation of an aqueous extract of blood cells of the assay. Apparently healthy subjects have a low circulating lipopolysaccharide activity, since it is neutralized and cleared rapidly. However, chronic endotoxemia is involved in the pathogenesis of many inflammation-driven conditions, especially cardiometabolic disorders. These include atherosclerotic cardiovascular diseases, obesity, liver diseases, diabetes, and metabolic syndrome, where endotoxemia has been recognized as a risk factor. The main source of endotoxemia is thought to be the gut microbiota. However, the oral dysbiosis in periodontitis, which is typically enriched with gram-negative bacterial species, may also contribute to endotoxemia. As endotoxemia is associated with an increased risk of cardiometabolic disorders, lipopolysaccharide could be considered as a molecular link between periodontal microbiota and cardiometabolic diseases., (© 2022 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.)

Background: Dental infections are frequent and have recently been implicated as a possible risk factor for Alzheimer's disease (AD). Despite a lack of studies investigating orofacial pain in this patient group, dental conditions are known to be a potential cause of pain and to affect quality of life and disease progression., Objectives: To evaluate oral status, mandibular function and orofacial pain in patients with mild AD versus healthy subjects matched for age and gender., Methods: Twenty-nine patients and 30 control subjects were evaluated. The protocol comprised a clinical questionnaire and dental exam, research diagnostic criteria for temporomandibular disorders, the McGill Pain Questionnaire, the decayed, missing, and filled teeth index, and included a full periodontal evaluation. AD signs and symptoms as well as associated factors were evaluated by a trained neurologist., Results: A higher prevalence of orofacial pain (20.7%, p < 0.001), articular abnormalities in temporomandibular joints (p < 0.05), and periodontal infections (p = 0.002) was observed in the study group compared to the control group., Conclusion: Orofacial pain and periodontal infections were more frequent in patients with mild AD than in healthy subjects. Orofacial pain screening and dental and oral exams should be routinely performed in AD patients in order to identify pathological conditions that need treatment thus improving quality of life compromised due to dementia.

Atherosclerotic cardiovascular diseases (ACVD) and oral infections such as periodontal disease, dental caries, and apical periodontitis are diseases that affect a great portion of the worldwide population. Both are complex in nature and several studies show that they share etiological factors but a causal relationship between them has not been yet established due to the lack of well-designed clinical trials. Many studies in the recent years show convincing evidence of different mechanisms that might be involved in this association including chronic inflammation and immune response. However, some of these mechanisms are controversial because of confounding factors. It has been suggested that maladaptive inflammatory reactivity, determined in part by single nucleotide polymorphisms (SNPs) in pathway genes, could influence the association between oral infections, and cardiovascular diseases as pleiotropic genes. That is, these conditions could be outcomes of similar inflammatory pathways. Phenomics, the study of the changes in phenotypes or traits considering environmental variables and genetics is efficient in assessing and determining pleiotropic genes. Future research should focus on analyzing a combination of oral inflammatory conditions instead of focusing on one inflammatory phenotype alone and consider pleiotropy as a mechanistic contributor for these associations. Further, prospective observational studies seeking to follow the development of oral disease and subclinical ACVD will foster the understanding of the impact of oral health on general systemic health. Lastly, to demonstrate that oral infections would increase risk for subclinical ACVD development, clinical trials proposing to treat those infections considering genetic background and all other confounders are needed. [ABSTRACT FROM AUTHOR]

Personalized Oral Healthcare has recently become the new trend word in medicine and dentistry. In this context, saliva diagnostics using various biomarkers seem to be the gateway to personalized dental diagnostics and therapy. But the terminology is not (yet) uniformly defined, furthermore it is unclear to what extent which salivary markers play a relevant role in the therapeutic decision making. In this Scoping Review, an electronic search was conducted in PubMed and Web of Science databases using medical subject headings (MESH terms) “saliva”, “biomarker”, “personality/persons”, and “dentistry”. Only human studies were included, in which repeated salivary measurements were performed to analyze monitoring effects with at least ten patients per group. PRISMA-ScR and Tricco guidelines were followed: (i) to examine what salivary biomarkers have been explored in terms of personalized oral healthcare and precision dentistry, (ii) to investigate the clinical relevance for oral health and its correlation to systemic health, and (iii) to summarize an outlook for future developments based on these results. Out of 899 studies, a total of 57 were included for data extraction in this Scoping Review, mainly focusing on periodontal therapy and patient monitoring. Salivary biomarkers have shown the potential to change the field of dentistry in all dental disciplines as a key for personalized workflows. The increasing interest in dental research is obvious, demonstrated by the growing number of publications in recent years. At this time, however, the predominant discipline is periodontology, which allows biomarker-based monitoring of the disease prevention and progression. The studies included showed heterogeneous methods using manifolds biomarkers. Therefore, no uniformly accepted concept can be presented today. Further clinical research with well-defined outcomes including standardized procedures is necessary.

IntroductionOral infectious diseases are common chronic oral diseases characterized by a chronic inflammatory condition. We investigated chronic oral diseases as potential risk factors for systemic chronic diseases, diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis, and Crohn's disease, as well as severe psychotic and other severe mental disorders.MethodsThe cohort comprised 68,273 patients aged ≥ 29 years with at least one dental visit to the Helsinki City Health Services between 2001 and 2002. The cohort was linked to the data on death (Statistics Finland), cancer (Finnish Cancer Registry), and drug reimbursement (Finnish Social Insurance Institution) and followed until death or the end of 2013. The outcomes of interest were the incidences of chronic diseases measured starting with special refund medication, which means Social Insurance Institution partly or fully reimburses medication costs. Outcomes of interest were diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis and Crohn's disease, and severe mental disorders.ResultsThe mean follow-up time was 9.8 years. About 25% of the study population had periodontitis, 17% caries, over 70% apical periodontitis, and 9%

Several links between chronic liver disease and oral health have been described and are discussed in this narrative review. Oral manifestations such as lichen planus, ulcers, xerostomia, erosion and tongue abnormalities seem to be particularly prevalent among patients with chronic liver disease. These may be causal, coincidental, secondary to therapeutic interventions, or attributable to other factors commonly observed in liver disease patients. In addition, findings from both experimental and epidemiological studies suggest that periodontitis can induce liver injury and contribute to the progression of chronic liver disease through periodontitis-induced systemic inflammation, endotoxemia, and gut dysbiosis with increased intestinal translocation. This has brought forward the hypothesis of an oral-gut-liver axis. Preliminary clinical intervention studies indicate that local periodontal treatments may lead to beneficial liver effects, but more human studies are needed to clarify if treatment of periodontitis truly can halt or reverse progression of liver disease and improve liver-related outcomes.

Cryptobacterium curtum Nakazawa et al. 1999 is the type species of the genus, and is of phylogenetic interest because of its very distant and isolated position within the family Coriobacteriaceae. C. curtum is an asaccharolytic, opportunistic pathogen with a typical occurrence in the oral cavity, involved in dental and oral infections like periodontitis, inflammations and abscesses. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of the actinobacterial family Coriobacteriaceae, and this 1,617,804 bp long single replicon genome with its 1364 protein-coding and 58 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project.

Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients.

Background and Objective Periodontal disease pathogenesis is comprised of the complex inflammatory immune response to oral bacterial dysbiosis. Like other inflammatory diseases, there is sexual dimorphism evident in periodontal diseases. During periodontitis, inflammatory chemokines direct neutrophils to migrate to the site of infection to neutralize the pathogen. Interestingly, these same chemokines are also involved in regulating pathogen-induced osteoclast formation. Previous reports show differences in bone turnover and lymphocyte recruitment between sexes. We hypothesize that chemokine expression is differentially regulated by sex and thus results in differential osteoclast formation. Material and Methods Male and female mice were utilized to isolate neutrophils based on expression of Ly6G-specific, as well as defined osteoclast progenitors. Cells were stimulated with lipopolysaccharide ( LPS; 100 ng/mL) then analyzed for neutrophil infiltration and gene expression. Defined osteoclast progenitors were primed: macrophage-colony stimulating factor (25 ng/mL), receptor activator of NF-κB ligand (50 ng/mL), then stimulated with LPS. Osteoclasts were enumerated via TRAP stain and mRNA isolated for gene expression analysis via quantitative polymerase chain reaction. Results In response to LPS, male neutrophils in vitro respond with increased chemokine expression and significantly more osteoclast formed in response to LPS compared to females. Conclusions Findings support observations in humans regarding a sexual dimorphism in oral bacterial infections of alveolar bone loss. Males have a strong inflammatory response to bacterial infection, resulting in increased inflammatory microenvironment, reduced pathogenic bacteria clearance and increased osteoclast-driven bone loss in response to differential expression of key chemokines. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory conditions the activation of endogenous degradation pathways mediated by immune responses leads to the release of destructive cellular molecules from both resident and immigrant cells. Matrix metalloproteinases (MMPs) and their regulators can activate each other and play an important role in immune response via degrading extracellular matrix components and modulating cytokines and chemokines. The action of MMPs is required for immigrant cell recruitment at the site of inflammation. Stimulated neutrophils represent the major pathogen-fighting immune cells that upregulate expression of several proteinases and oxidative enzymes, which can degrade extracellular matrix components (e.g. MMP-8, MMP-9 and neutrophil elastase). The activity of MMPs is regulated by endogenous inhibitors and/or candidate MMPs (e.g. MMP-7). The balance between MMPs and their inhibitors is thought to mirror the proteolytic burden. Thus, neutrophil-derived biomarkers, including myeloperoxidase, may activate proteolytic destructive cascades that are involved in subsequent immune-pathological events associated with both periodontitis and CHD. Here, we review the existing studies on the contribution of MMPs and their regulators to the infection-related pathology. Also, we discuss the possible proteolytic involvement and role of neutrophil-derived enzymes as an etiological link between chronic periodontitis and CHD. [ABSTRACT FROM AUTHOR]

Brain abscesses are rare but potentially deadly complications of odontogenic infections. This phenomenon has been described mainly in the form of case reports, as large-scale studies are difficult to perform. We compiled a total of 60 previously published cases of such a complication to investigate the predisposing factors, microbiology, and clinical outcomes of intracranial abscesses of odontogenic origin. A systematic review of the literature using the PubMed database was performed. Men accounted for 82.1% of cases, and the mean age was 42.1 years. Caries with periapical involvement and periodontitis were the two most common intra-oral sources, and wisdom tooth extraction was the most common preceding dental procedure. In 56.4% of cases, there were obvious signs of dental disease prior to development of intracranial infection. Commonly implicated microorganisms included Streptococcus viridans (especially the anginosus group), Actinomyces, Peptostreptococcus, Prevotella, Fusobacterium, Aggregatibacter actinomycetemcomitans and Eikenella corrodens. There was an 8.3% mortality rate. Intracranial abscesses can form anywhere within the brain, and appear unrelated to the side of dental involvement. This suggests that hematogenous spread is the most likely route of dissemination. [ABSTRACT FROM AUTHOR]

Introduction We aimed to investigate the relationship between blood profile and histologic findings in both apical periodontitis (AP) and periodontal disease (PD) associated with diabetes. Methods Wistar rats (N = 80) were assigned to the following 8 groups: control, AP, PD, AP associated with PD, diabetes, diabetes with AP, diabetes with PD, and diabetes with AP and PD. Diabetes mellitus (DM) was induced with streptozotocin, AP was induced by exposure to the oral environment, and PD was induced using periodontal ligature. After 30 days, blood samples were collected, and the rats were euthanized. Subsequently, the maxillae were processed for light microscopy. Hematologic examinations were conducted to determine the total number of erythrocytes and leukocytes, erythrocyte constant, and blood glucose level. One-way analysis of variance and Kruskal-Wallis tests were used for statistical analysis, and the significance was set at P < .05. Results A significant correlation was found between the histologic findings and blood parameters. Conclusions In conclusion, diabetes accelerated the development and progression of AP and PD in the rats and caused an increase in the average erythrocyte volume as well as the leukocyte and neutrophil counts. Oral infections increase the total number of leukocytes, the number of neutrophils and lymphocytes, and blood glucose concentrations in DM rats. [ABSTRACT FROM AUTHOR]

Several links between chronic liver disease and oral health have been described and are discussed in this narrative review. Oral manifestations such as lichen planus, ulcers, xerostomia, erosion and tongue abnormalities seem to be particularly prevalent among patients with chronic liver disease. These may be causal, coincidental, secondary to therapeutic interventions, or attributable to other factors commonly observed in liver disease patients. In addition, findings from both experimental and epidemiological studies suggest that periodontitis can induce liver injury and contribute to the progression of chronic liver disease through periodontitis-induced systemic inflammation, endotoxemia, and gut dysbiosis with increased intestinal translocation. This has brought forward the hypothesis of an oral-gut-liver axis. Preliminary clinical intervention studies indicate that local periodontal treatments may lead to beneficial liver effects, but more human studies are needed to clarify if treatment of periodontitis truly can halt or reverse progression of liver disease and improve liver-related outcomes. [ABSTRACT FROM AUTHOR]

Archaea, organisms that make up the third domain of cellular life are members of the human oral microflora. They are strikingly less diverse than oral bacteria and appear to be relatively rare with respect to their numerical abundance. Since they have been exclusively found in association with oral infections such as periodontitis and apical periodontitis and given their unique physiology and energy metabolism, it is highly plausible that they are more than just secondary colonizers of infected areas, but instead are actively involved in the overall poly-microbial infection process. Conversely, it is a highly challenging task to clearly demonstrate their possible active participation — mostly due to the difficulty to grow them in routine microbiology laboratories. This current review points out the importance for understanding the medical impact of methanogens and aims at devising strategies for elucidating the true function of archaea in the oral ecosystem. [ABSTRACT FROM AUTHOR]

Background: Plasma antibody measurements of antibody levels to periodontal pathogens may be used to support diagnosis, disease activity, classification, and prognosis of periodontitis. Objective: The aim of this study was to investigate the long-term stability of plasma antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Design: Plasma immunoglobulin G (IgG) antibody levels against the pathogens were analyzed annually during 15 years from 21 voluntary subjects, whose periodontal status was not known at the point of selection. The total number of plasma samples was 315. In connection of the last sampling, the clinical and radiographic periodontal status was examined. Pooled bacterial samples from periodontal pockets, as well as salivary samples were collected for A. actinomycetemcomitans and P. gingivalis detection, and antibody determinations, respectively. According to the clinical status, six subjects had periodontitis, whereas 15 did not. Results: Plasma IgG-class antibody levels to periodontal pathogens remained extremely stable during the 15-year period and no significant (p>0.05) intra-individual variations were observed. Retrospectively, the average plasma IgG antibody levels against A. actinomycetemcomitans and P. gingivalis were 1.6-2.3 (p<0.05) and 1.4-1.7 (p<0.05) fold higher in the subjects with periodontitis than those without, respectively, during the whole 15-year tracking. As expected, at the time of the periodontal examination the plasma and salivary IgG antibody levels were associated both with periodontitis and bacterium-positivity. Conclusions: Plasma IgG levels against A. actinomycetemcomitans and P. gingivalis are extremely stable during 15 years both in subjects with and without periodontitis. [ABSTRACT FROM AUTHOR]

Oral spirochaetes, which are small-, medium- or large-sized, include species of the genus Treponema, many of which have not yet been cultured. They are found in root canal infections, pericoronitis, gingivitis and periodontitis, constituting up to 10% of the flora in endodontic abscesses, 30% in acute necrotizing ulcerative gingivitis, and 56% in advanced marginal periodontitis. The strong proteolytic activity of these organisms probably make them causes of infection rather than consequences. Being able to penetrate tissue, they bring their enzymes, meta-bolic products, and endatoxins, in direct contact with target cells. This may perturb essential functions of host cells and immunoglobulins. Enzyme activities may also help fulfil the complex growth requirements of spirochaetes in vivo. Reaction between infected periodontal tissue and monoclonal antibodies to Treponema pallidum has suggested that uncharacterized pathogen-related oral spirochaetes have surface structures and functions analogue to this well recognized pathogen. This warrants a more intensified search for the role of spirochactes in oral infections. [ABSTRACT FROM AUTHOR]

Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients. [ABSTRACT FROM AUTHOR]