Potential mechanisms between periodontitis and Alzheimer's disease: a scoping review.

Background: Research has suggested 2 potential mechanisms by which the periodontal inflammatory response may communicate to distant organs: 1) direct translocation of periodontal bacteria from the oral cavity to another organ system; and 2) inflammation as a result of metastatic periodontal inflammation. The purpose of this scoping review is to explore these mechanisms as potential mediators between periodontitis and Alzheimer's disease. Methods: A reiterative literature search of peer-reviewed articles was performed in the PubMed and Scopus databases using keywords or combinations such as Alzheimer's disease AND periodontitis OR periodontal disease AND inflammation. Results: A total of 777 articles were identified. After eliminating duplicates and reviewing titles and abstracts, 84 articles were selected for full-text review. Following full-text review, 19 articles met the eligibility criteria for the study. Discussion: The review of the literature highlights how periodontitis may contribute to neuroinflammation by the introduction of periodontal bacteria and/or proinflammatory cytokines locally produced at the periodontium. Conclusion: Inflammation is an important mechanism in the onset and progression of both periodontitis and Alzheimer's disease. Nevertheless, further studies are necessary to better understand the multifactorial pathogenesis of Alzheimer's disease.

Contexte: La recherche a suggéré 2 possibilités de mécanismes par lesquels la réponse inflammatoire parodontale peut communiquer avec des organes distants : 1) la translocation directe des bactéries parodontales de la cavité buccale vers un autre système organique; et 2) l'inflammation découlant d'une inflammation parodontale métastatique. Le but de cet examen de la portée est d'explorer ces mécanismes en tant que médiateurs potentiels entre la parodontite et la maladie d'Alzheimer. Méthodologie: Une recherche documentaire réitérative d'articles évalués par des pairs a été effectuée dans les bases de données PubMed et Scopus en utilisant les mots-clés ou des combinaisons de mots-clés tels que maladie d'Alzheimer ET parodontite OU maladie parodontale ET inflammation (en anglais). Résultats: Un total de 777 articles a été répertorié. Après avoir éliminé les doublons et examiné les titres et les résumés, 84 articles ont été sélectionnés pour être examinés dans leur intégralité. À la suite de l'examen du texte complet, 19 articles répondaient aux critères d'admissibilité de l'étude. Discussion: L'analyse documentaire souligne comment la parodontite peut contribuer à la neuroinflammation en introduisant des bactéries parodontales ou des cytokines pro-inflammatoires produites localement au niveau du parodonte. Conclusion: L'inflammation est un mécanisme important dans l'apparition et la progression à la fois de la parodontite et de la maladie d'Alzheimer. Néanmoins, d'autres études sont nécessaires pour mieux comprendre la pathogenèse multifactorielle de la maladie d'Alzheimer.

Antibodies against Periodontal Microorganisms and Cognition in Older Adults.

INTRODUCTION: Markers of poor oral health are associated with impaired cognition and higher risk of Alzheimer disease (AD) and thus may help predict AD. OBJECTIVES: The aim of this study was to evaluate the cross-sectional association between empirically derived groups of 19 IgG antibodies against periodontal microorganisms and cognition in middle-aged and older adults. METHODS: The study population consisted of participants of the third National Health and Nutrition Examination Survey (NHANES III) (1988 to 1994), who were 60 y and older, among whom cognition and IgG antibodies against 19 periodontal microorganisms were measured (N = 5,162). RESULTS: In multivariable quantile regression analyses, the Orange-Red (Prevotella melaninogenica, Prevotella intermedia, Prevotella nigrescens, Porphyromonas gingivalis) and Yellow-Orange (Staphylococcus intermedius, Streptococcus oralis, Streptococcus mutans, Fusobacterium nucleatum, Peptostreptococcus micros, Capnocytophaga ochracea) cluster scores were negatively associated with cognition. A 1-unit higher cluster score for the Orange-Red cluster was associated on average with a lower cognitive score (ß for 30th quantile = -0.2640; 95% confidence interval [CI], -0.3431 to -0.1848). Similarly, a 1-unit higher score for the Yellow-Orange cluster was associated with a lower cognitive score (ß for 30th quantile = -0.2445; 95% CI, -0.3517 to -0.1372). CONCLUSION: Groups of IgG antibodies against periodontal microorganisms were associated with lower cognition among free living adults 60 years and older, who were previously undiagnosed with cognitive impairment. Though poor oral health precedes the development of dementia and AD, oral health information is currently not used, to our knowledge, to predict dementia or AD risk. Combining our findings with current algorithms may improve risk prediction for dementia and AD. KNOWLEDGE TRANSLATION STATEMENT: IgG antibodies against periodontal microorganisms were associated with lower cognition among adults 60 years and older previously undiagnosed with cognitive impairment. Periodontal disease may predict cognition among older adults.

Impact of Oral Microbiome in Periodontal Health and Periodontitis: A Critical Review on Prevention and Treatment.

The skin, oral cavity, digestive and reproductive tracts of the human body harbor symbiotic and commensal microorganisms living harmoniously with the host. The oral cavity houses one of the most heterogeneous microbial communities found in the human organism, ranking second in terms of species diversity and complexity only to the gastrointestinal microbiota and including bacteria, archaea, fungi, and viruses. The accumulation of microbial plaque in the oral cavity may lead, in susceptible individuals, to a complex host-mediated inflammatory and immune response representing the primary etiological factor of periodontal damage that occurs in periodontitis. Periodontal disease is a chronic inflammatory condition affecting about 20-50% of people worldwide and manifesting clinically through the detection of gingival inflammation, clinical attachment loss (CAL), radiographic assessed resorption of alveolar bone, periodontal pockets, gingival bleeding upon probing, teeth mobility and their potential loss in advanced stages. This review will evaluate the changes characterizing the oral microbiota in healthy periodontal tissues and those affected by periodontal disease through the evidence present in the literature. An important focus will be placed on the immediate and future impact of these changes on the modulation of the dysbiotic oral microbiome and clinical management of periodontal disease.

Correlation of HMGB1, PON-1, MCP-1, and Periodontal P. gingivalis with Amniotic Fluid Fecal Dye.

BACKGROUND: This paper aims to investigate the correlation between high mobility group protein-1 (HMG-b1), antioxidant enzyme-1 (paraoxon-1, PON-1), monocyte chemoattractant protein-1 (monocyte chemoattractant protein-1, MCP-1), P. gingivalis, and MSAF. MATERIALS AND METHODS: The total sample size comprised of 73 cases in both groups. These patients were further subdivided into 2 groups: the MSAF group and the control group. 38 women were in the MSAF group and 35 women with term amniotic fluid serum were in the control group. The MSAF group was selected as a full-term singleton amniotic fluid fecal infection group. Clinical data were collected, and specimens were collected. Fecal staining of amniotic fluid and full-term amniotic fluid removes the placenta and umbilical cord blood. The expression of HMGB1 in the placenta was observed by immune-histochemical staining of MSAF and control groups. The content of PON-1 in cord blood was determined by ELISA. RESULTS: Correlation between maternal and neonatal clinical data and MSAF was done; MSAF group mean gestational age was 41.38 ± 1.40 weeks; control group mean gestational age was 39.20 ± 1.24 weeks. This study found no correlation between the birth weight, maternal age, sex, first/transmaternal, hyperthyroidism, hypothyroidism, and anemia between the MSAF and control group with nonsignificant P value (P > 0.05). However, the fatal age, gestational diabetes, gestational hypertension, umbilical cord abnormalities, placental abnormalities, and neonatal asphyxia factors were statistically different with a significant P value of <0.05 between both groups. HMGB1 and Periodontal P. gingivalis are mostly expressed in placental trophoblast, vascular endothelial cells, and amniotic epithelial and interstitial cells. After HE staining of 72 placentas by HE in MSAF and control, 6 had acute chorioamnionitis (5.1 control), 32 had chronic (23.9), 35 had abnormal placentas, and three in MSAF had chorionic columnar metaplasia. In immune-histochemistry experiments, the HMGB1 expression intensity of placental tissue was higher in the MSAF group (P < 0.05); however, the level of PON-1 was lower in the MSAF group as compared to the controls (P < 0.05). CONCLUSIONS: Gestational age and placental abnormalities are clinical high-risk factors for MSAF. HMGB1, PON-1, MCP-1, and Periodontal P. gingivalis may be involved in the development of MSAF, suggesting an oxidative/antioxidant imbalance with inflammation, and may be one of the mechanisms for MSAF development.

Electronic Cigarette Use Promotes a Unique Periodontal Microbiome.

Electronic cigarettes (e-cigs) have become prevalent as an alternative to conventional cigarette smoking, particularly in youth. E-cig aerosols contain unique chemicals which alter the oral microbiome and promote dysbiosis in ways we are just beginning to investigate. We conducted a 6-month longitudinal study involving 84 subjects who were either e-cig users, conventional smokers, or nonsmokers. Periodontal condition, cytokine levels, and subgingival microbial community composition were assessed, with periodontal, clinical, and cytokine measures reflecting cohort habit and positively correlating with pathogenic taxa (e.g., Treponema, Saccharibacteria, and Porphyromonas). α-Diversity increased similarly across cohorts longitudinally, yet each cohort maintained a unique microbiome. The e-cig microbiome shared many characteristics with the microbiome of conventional smokers and some with nonsmokers, yet it maintained a unique subgingival microbial community enriched in Fusobacterium and Bacteroidales (G-2). Our data suggest that e-cig use promotes a unique periodontal microbiome, existing as a stable heterogeneous state between those of conventional smokers and nonsmokers and presenting unique oral health challenges. IMPORTANCE Electronic cigarette (e-cig) use is gaining in popularity and is often perceived as a healthier alternative to conventional smoking. Yet there is little evidence of the effects of long-term use of e-cigs on oral health. Conventional cigarette smoking is a prominent risk factor for the development of periodontitis, an oral disease affecting nearly half of adults over 30 years of age in the United States. Periodontitis is initiated through a disturbance in the microbial biofilm communities inhabiting the unique space between teeth and gingival tissues. This disturbance instigates host inflammatory and immune responses and, if left untreated, leads to tooth and bone loss and systemic diseases. We found that the e-cig user's periodontal microbiome is unique, eliciting unique host responses. Yet some similarities to the microbiomes of both conventional smokers and nonsmokers exist, with strikingly more in common with that of cigarette smokers, suggesting that there is a unique periodontal risk associated with e-cig use.

Oral streptococci subvert the host innate immune response through hydrogen peroxide.

In periodontal health, oral streptococci constitute up to 80% of the plaque biofilm. Yet, destructive inflammatory events of the periodontium are rare. This observation suggests that oral streptococci may possess mechanisms to co-exist with the host. However, the mechanisms employed by oral streptococci to modulate the innate immune response have not been well studied. One of the key virulence factors produced by oral streptococci is hydrogen peroxide (H2O2). In mammalian cells, H2O2 triggers the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key pathway mediating antioxidant defence. This study aimed to determine (1) if H2O2 producing oral streptococci activated the Nrf2 pathway in macrophages, and (2) if the activation of Nrf2 influenced the innate immune response. We found that oral streptococci downregulated the innate immune response in a H2O2 dependent manner through the activation of the Nrf2. The activation of the Nrf2 signalling pathway led to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFĸB), the key transcription factor regulating pro-inflammatory response. This study showed for the first time that oral streptococci are unlikely passive bystanders but could play an active role in the maintenance of periodontal health by preventing overt inflammation.

Periodontitis and Gestational Diabetes Mellitus: A Potential Inflammatory Vicious Cycle.

Periodontitis is a chronic inflammatory immune disease associated with a dysbiotic state, influenced by keystone bacterial species responsible for disrupting the periodontal tissue homeostasis. Furthermore, the severity of periodontitis is determined by the interaction between the immune cell response in front of periodontitis-associated species, which leads to the destruction of supporting periodontal tissues and tooth loss in a susceptible host. The persistent bacterial challenge induces modifications in the permeability and ulceration of the sulcular epithelium, which facilitates the systemic translocation of periodontitis-associated bacteria into distant tissues and organs. This stimulates the secretion of pro-inflammatory molecules and a chronic activation of immune cells, contributing to a systemic pro-inflammatory status that has been linked with a higher risk of several systemic diseases, such as type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). Although periodontitis and GDM share the common feature of systemic inflammation, the molecular mechanistic link of this association has not been completely clarified. This review aims to examine the potential biological mechanisms involved in the association between periodontitis and GDM, highlighting the contribution of both diseases to systemic inflammation and the role of new molecular participants, such as extracellular vesicles and non-coding RNAs, which could act as novel molecular intercellular linkers between periodontal and placental tissues.

Study of microbiocenosis of canine dental biofilms.

Dental biofilm is a complex microbial community influenced by many exogenous and endogenous factors. Despite long-term studies, its bacterial composition is still not clearly understood. While most of the research on dental biofilms was conducted in humans, much less information is available from companion animals. In this study, we analyzed the composition of canine dental biofilms using both standard cultivation on solid media and amplicon sequencing, and compared the two approaches. The 16S rRNA gene sequences were used to define the bacterial community of canine dental biofilm with both, culture-dependent and culture-independent methods. After DNA extraction from each sample, the V3-V4 region of the 16S rRNA gene was amplified and sequenced via Illumina MiSeq platform. Isolated bacteria were identified using universal primers and Sanger sequencing. Representatives of 18 bacterial genera belonging to 5 phyla were isolated from solid media. Amplicon sequencing largely expanded this information identifying in total 284 operational taxonomic units belonging to 10 bacterial phyla. Amplicon sequencing revealed much higher diversity of bacteria in the canine dental biofilms, when compared to standard cultivation approach. In contrast, cultured representatives of several bacterial families were not identified by amplicon sequencing.

Bacteriological Evaluation of Gingival Crevicular Fluid in Teeth Restored Using Fixed Dental Prostheses: An In Vivo Study.

The present in vivo study determined the microbiological counts of the gingival crevicular fluid (GCF) among patients with fixed dental prostheses fabricated using three different techniques. A total of 129 subjects were divided into three study groups: first, cobalt-chrome-based, metal-ceramic prostheses fabricated by the conventional method (MC, n = 35); the second group consisted of cobalt-chrome-based, metal-ceramic prostheses fabricated by the computer-aided design and computer-aided manufacturing (CAD/CAM) technique (CC-MC, n = 35); the third group comprised zirconia-based ceramic prostheses fabricated using the CAD/CAM technique (CC-Zr, n = 35). The control consisted of 24 patients using prostheses fabricated with either MC, CC-MC, or CC-Zr. The GCF was obtained from the subjects before treatment, and 6 and 12 months after the prosthetic treatment. Bacteriological and bacterioscopic analysis of the GCF was performed to analyze the patients' GCF. The data were analyzed using SPSS V20 (IBM Company, Chicago, IL, USA). The number of microorganisms of the gingival crevicular fluid in all groups at 12 months of prosthetic treatment reduced dramatically compared with the data obtained before prosthetic treatment. Inflammatory processes in the periodontium occurred slowly in the case of zirconium oxide-based ceramic constructions due to their biocompatibility with the mucous membranes and tissues of the oral cavity as well as a reduced risk of dental biofilm formation. This should be considered by dentists and prosthodontists when choosing restoration materials for subjects with periodontal pathology.

Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation.

Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral microbiome in periodontitis in relation to disease severity and systemic inflammation. The saliva and subgingival microbiome from periodontal pocket samples of patients with severe (n = 12) and mild periodontitis (n = 13) were analyzed using metagenomic shotgun sequencing. The taxa and pathways abundances were quantified. The diversity was assessed and the abundances to phenotype associations were performed using ANCOM and linear regression. A panel of inflammatory markers was measured in blood and was associated with taxa abundance. The microbial diversity and species richness did not differ between severe and mild periodontitis in either saliva or periodontal pockets. However, there were significant differences in the microbial composition between severe and mild periodontitis in the subgingival microbiome (i.e., pocket samples) and, in a lower grade, in saliva, and this is positively associated with systemic inflammatory markers. The "red complex" and "cluster B" abundances in periodontal pockets were strongly associated with inflammatory markers interleukin-6 and the white blood cell count. Our data suggest that systemic inflammation in severe periodontitis may be driven by the oral microbiome and may support the indirect (inflammatory) mechanism for the association between periodontitis and cardiovascular disease.

Intersection between macrophages and periodontal pathogens in periodontitis.

Periodontitis is a chronic infectious disease characterized by loss of periodontal attachment and resorption of alveolar bone. Dysregulated oral microbial community is the initial factor of periodontitis and causes excessive infiltration of immune cells in periodontal tissues. Macrophage, as an important part of the innate immune system, interacts continually with oral pathogens. Macrophages can recognize and phagocytize pathogens and apoptotic neutrophils and produce the specialized pro-resolving mediators (SPMs) playing an important role in maintaining the homeostasis of tissue microenvironment. However, macrophages may also induce abnormal immune responses with the overstimulation from pathogens, leading to the destruction of periodontal tissues and alveolar bone. Looking for targeted drugs that can regulate the activities of oral pathogens and the functions of macrophages provides a new idea for periodontitis treatment. This review summarizes the interaction between macrophages and periodontal pathogens in periodontitis, focusing on the pro-inflammation and anti-inflammation phenotypes of macrophages, and briefly concludes potential new methods of periodontitis therapy targeted at oral pathogens and macrophages.

Two Zn(II)-based Coordination Polymers: Treatment Activity on Chronic Periodontitis by Inhibiting the Relative Expression of the Porphyria gingivalis Survival Gene.

Two mixed-ligand complexes on the basis of L ligand [L = 3,6-bis(imidazol-1-yl)pyridazine] have been prepared under the solvothermal reaction conditions via the Zn(II) salts reacting with the ligands of L in the existence of two positional isomerous carboxylic acid ligands and their chemical formula respectively are [Zn5(L)(1,2-BDC)4(µ3-OH)2] n (1, 1,2-H2BDC = 1,2-benzenedicarboxylic acid ) and {[Zn4(L)2(1,3-HBDC) (1,3-BDC)(µ3-OH)4]·ClO4·3H2O} n (2, 1,3-H2BDC = 1,3-benzenedicarboxylic acid). The inhibitory influence of the two compounds against the inflammatory response in periodontium was evaluated by measuring the inflammatory cytokines releasing with ELISA detection kit. The results of ELISA assay indicated that compound 1 showed much stronger inhibitory influences than compound 2 against the inflammatory cytokines releasing. In addition to this, the suppression activity of the compounds against the survival gene of Porphyria gingivalis was detected via the real time Reverse Transcription-Polymerase Chain Reaction, and the results suggested that compound 1 could evidently suppresses the survival gene expression of Porphyria gingivalis, which is much better than the biological activity of compound 2. Above all, compound 1 was more outstanding than compound 2 on chronic periodontitis treatment by inhibiting the Porphyria gingivalis survival.

Comparing the sub-gingival levels of Cytomegalovirus, Epstein-Barr virus, Porphyromonas gingivalis in human immunodeficiency virus-1 seropositive patients with and without antiretroviral therapy.

OBJECTIVES: The effect of antiretroviral therapy (ART) on the oral pathogenic microbes in human immunodeficiency virus-1 seropositive patients remains relatively unexplored. Thus, the present study assessed the effect of ART on the sub-gingival levels of 3 pathogenic microbes. MATERIALS AND METHODS: The study groups consisted of 60 human immunodeficiency virus-1 seropositive patients divided into 3 groups of 20 each. Group 1 had periodontitis and did not start with the ART. Group 2 had periodontitis and started with ART (Tenofovir Disoproxil Fumarate 300 mg + Lamivudine 300 mg + Efavirenz 600 mg) at least 6 months before the study. Group 3 with normal periodontium, and have not started ART. The sub-gingival loads of Cytomegalovirus, Epstein-Barr virus, and the Porphyromonas gingivalis levels were assessed, along with the CD4 counts. RESULTS: The cytomegalovirus load was highest in group 1, followed by groups 2, and 3 (p-value of 0.271). The Epstein-Barr load was highest for group 2, followed by group 3, and 1 (p-value of 0.022). The P.gingivalis load was highest in group 2, followed by groups 1 and 3, (p-value of 0.028). The Epstein-Barr and Cytomegalovirus counts were significantly higher (p-value < 0.02) when the CD4 counts were less than 500 cells/cu3. CONCLUSION: ART did not cause any significant reduction in the sub-gingival levels of any of the 3 examined microbes. Given the lack of any significant effect on the sub-gingival microbial loads by the ART, human immunodeficiency virus patients may require additional anti-microbial agents and regular mechanical plaque removal to maintain their periodontal status.

The impact of smoking different tobacco types on the subgingival microbiome and periodontal health: a pilot study.

Smoking is a risk factor for periodontal disease, and a cause of oral microbiome dysbiosis. While this has been evaluated for traditional cigarette smoking, there is limited research on the effect of other tobacco types on the oral microbiome. This study investigates subgingival microbiome composition in smokers of different tobacco types and their effect on periodontal health. Subgingival plaques were collected from 40 individuals, including smokers of either cigarettes, medwakh, or shisha, and non-smokers seeking dental treatment at the University Dental Hospital in Sharjah, United Arab Emirates. The entire (~ 1500 bp) 16S rRNA bacterial gene was fully amplified and sequenced using Oxford Nanopore technology. Subjects were compared for the relative abundance and diversity of subgingival microbiota, considering smoking and periodontal condition. The relative abundances of several pathogens were significantly higher among smokers, such as Prevotella denticola and Treponema sp. OMZ 838 in medwakh smokers, Streptococcus mutans and Veillonella dispar in cigarette smokers, Streptococcus sanguinis and Tannerella forsythia in shisha smokers. Subgingival microbiome of smokers was altered even in subjects with no or mild periodontitis, probably making them more prone to severe periodontal diseases. Microbiome profiling can be a useful tool for periodontal risk assessment. Further studies are recommended to investigate the impact of tobacco cessation on periodontal disease progression and oral microbiome.

Regulation of Anti-Apoptotic SOD2 and BIRC3 in Periodontal Cells and Tissues.

The aim of the study was to clarify whether orthodontic forces and periodontitis interact with respect to the anti-apoptotic molecules superoxide dismutase 2 (SOD2) and baculoviral IAP repeat-containing protein 3 (BIRC3). SOD2, BIRC3, and the apoptotic markers caspases 3 (CASP3) and 9 (CASP9) were analyzed in gingiva from periodontally healthy and periodontitis subjects by real-time PCR and immunohistochemistry. SOD2 and BIRC3 were also studied in gingiva from rats with experimental periodontitis and/or orthodontic tooth movement. Additionally, SOD2 and BIRC3 levels were examined in human periodontal fibroblasts incubated with Fusobacterium nucleatum and/or subjected to mechanical forces. Gingiva from periodontitis patients showed significantly higher SOD2, BIRC3, CASP3, and CASP9 levels than periodontally healthy gingiva. SOD2 and BIRC3 expressions were also significantly increased in the gingiva from rats with experimental periodontitis, but the upregulation of both molecules was significantly diminished in the concomitant presence of orthodontic tooth movement. In vitro, SOD2 and BIRC3 levels were significantly increased by F. nucleatum, but this stimulatory effect was also significantly inhibited by mechanical forces. Our study suggests that SOD2 and BIRC3 are produced in periodontal infection as a protective mechanism against exaggerated apoptosis. In the concomitant presence of orthodontic forces, this protective anti-apoptotic mechanism may get lost.

Detection of periodontal microorganisms in coronary atheromatous plaque specimens of myocardial infarction patients: A systematic review and meta-analysis.

BACKGROUND: Microbial translocation from inflamed periodontal pockets into coronary atheroma via systemic circulation is one of the proposed pathways that links periodontitis and myocardial infarction (MI). The purpose of this systematic review is to determine the reported prevalence of periodontal microorganisms in coronary atheroma and/or aspirated clot samples collected from MI patients with periodontal disease. METHODOLOGY: The "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines were followed. Six databases were systematically searched using Medical Subject Headings/Index and Entree terms. After a thorough screening, fourteen publications spanning over ten years (2007-2017) were eligible for this systematic review and meta-analysis. RESULTS: Out of 14 included studies, 12 reported presence of periodontal bacterial DNA in coronary atherosclerotic plaque specimens. Overall, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were the most frequently detected periodontal bacterial species. Meta-analysis revealed that the prevalence of P. gingivalis was significantly higher than A. actinomycetemcomitans in coronary atheromatous plaque samples. Apart from periodontal microbes, DNA from a variety of other microbes e.g. Pseudomonas fluorescens, Streptococcus species, Chlamydia pneumoniae were also recovered from the collected samples. CONCLUSION: Consistent detection of periodontal bacterial DNA in coronary atheroma suggests their systemic dissemination from periodontal sites. It should further be investigated whether they are merely bystanders or induce any structural changes within coronary arterial walls.

Microbial Lipid A Remodeling Controls Cross-Presentation Efficiency and CD8 T Cell Priming by Modulating Dendritic Cell Function.

The majority of Gram-negative bacteria elicit a potent immune response via recognition of lipid A expressed on the outer bacterial membrane by the host immune receptor Toll-like receptor 4 (TLR4). However, some Gram-negative bacteria evade detection by TLR4 or alter the outcome of TLR4 signaling by modification of lipid A species. Although the role of lipid A modifications on host innate immunity has been examined in some detail, it is currently unclear how lipid A remodeling influences host adaptive immunity. One prototypic Gram-negative bacterium that modifies its lipid A structure is Porphyromonas gingivalis, an anaerobic pathobiont that colonizes the human periodontium and induces chronic low-grade inflammation that is associated with periodontal disease as well as a number of systemic inflammatory disorders. P. gingivalis produces dephosphorylated and deacylated lipid A structures displaying altered activities at TLR4. Here, we explored the functional role of P. gingivalis lipid A modifications on TLR4-dependent innate and adaptive immune responses in mouse bone marrow-derived dendritic cells (BMDCs). We discovered that lipid A 4'-phosphate removal is required for P. gingivalis to evade BMDC-dependent proinflammatory cytokine responses and markedly limits the bacterium's capacity to induce beta interferon (IFN-ß) production. In addition, lipid A 4'-phosphatase activity prevents canonical bacterium-induced delay in antigen degradation, which leads to inefficient antigen cross-presentation and a failure to cross-prime CD8 T cells specific for a P. gingivalis-associated antigen. We propose that lipid A modifications produced by this bacterium alter host TLR4-dependent adaptive immunity to establish chronic infections associated with a number of systemic inflammatory disorders.

Effect of Ligilactobacillus salivarius and Other Natural Components against Anaerobic Periodontal Bacteria.

In this present study, the bacteriostatic effect of Salistat SGL03 and the Lactobacillus salivarius strain contained in it was investigated in adults in in vivo and in vitro tests on selected red complex bacteria living in the subgingival plaque, inducing a disease called periodontitis, i.e., chronic periodontitis. Untreated periodontitis can lead to the destruction of the gums, root cementum, periodontium, and alveolar bone. Anaerobic bacteria, called periopathogens or periodontopathogens, play a key role in the etiopathogenesis of periodontitis. The most important periopathogens of the oral microbiota are: Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and others. Our hypothesis was verified by taking swabs of scrapings from the surface of the teeth of female hygienists (volunteers) on full and selective growth media for L. salivarius. The sizes of the zones of growth inhibition of periopathogens on the media were measured before (in vitro) and after consumption (in vivo) of Salistat SGL03, based on the disk diffusion method, which is one of the methods of testing antibiotic resistance and drug susceptibility of pathogenic microorganisms. Additionally, each of the periopathogens analyzed by the reduction inoculation method, was treated with L. salivarius contained in the SGL03 preparation and incubated together in Petri dishes. The bacteriostatic activity of SGL03 preparation in selected periopathogens was also analyzed using the minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests. The obtained results suggest the possibility of using the Salistat SGL03 dietary supplement in the prophylaxis and support of the treatment of periodontitis-already treated as a civilization disease.

Surfactin-Loaded ĸ-Carrageenan Oligosaccharides Entangled Cellulose Nanofibers as a Versatile Vehicle Against Periodontal Pathogens.

PURPOSE: Periodontitis is a chronic inflammatory disease associated with microbial accumulation. The purpose of this study was to reuse the agricultural waste to produce cellulose nanofibers (CNF) and further modification of the CNF with κ-carrageenan oligosaccharides (CO) for drug delivery. In addition, this study is focused on the antimicrobial activity of surfactin-loaded CO-CNF towards periodontal pathogens. MATERIALS AND METHODS: A chemo-mechanical method was used to extract the CNF and the modification was done by using CO. The studies were further proceeded by adding different quantities of surfactin [50 mg (50 SNPs), 100 mg (100 SNPs), 200 mg (200 SNPs)] into the carrier (CO-CNF). The obtained materials were characterized, and the antimicrobial activity of surfactin-loaded CO-CNF was evaluated. RESULTS: The obtained average size of CNF and CO-CNF after ultrasonication was 263 nm and 330 nm, respectively. Microscopic studies suggested that the CNF has a short diameter with long length and CO became cross-linked to form as beads within the CNF network. The addition of CO improved the degradation temperature, crystallinity, and swelling property of CNF. The material has a controlled drug release, and the entrapment efficiency and loading capacity of the drug were 53.15 ± 2.36% and 36.72 ± 1.24%, respectively. It has antioxidant activity and inhibited the growth of periodontal pathogens such as Streptococcus mutans and Porphyromonas gingivalis by preventing the biofilm formation, reducing the metabolic activity, and promoting the oxidative stress. CONCLUSION: The study showed the successful extraction of CNF and modification with CO improved the physical parameters of the CNF. In addition, surfactin-loaded CO-CNF has potential antimicrobial activity against periodontal pathogens. The obtained biomaterial is economically valuable and has great potential for biomedical applications.

Analysis of oral microbiome from fossil human remains revealed the significant differences in virulence factors of modern and ancient Tannerella forsythia.

BACKGROUND: Recent advances in the next-generation sequencing (NGS) allowed the metagenomic analyses of DNA from many different environments and sources, including thousands of years old skeletal remains. It has been shown that most of the DNA extracted from ancient samples is microbial. There are several reports demonstrating that the considerable fraction of extracted DNA belonged to the bacteria accompanying the studied individuals before their death. RESULTS: In this study we scanned 344 microbiomes from 1000- and 2000- year-old human teeth. The datasets originated from our previous studies on human ancient DNA (aDNA) and on microbial DNA accompanying human remains. We previously noticed that in many samples infection-related species have been identified, among them Tannerella forsythia, one of the most prevalent oral human pathogens. Samples containing sufficient amount of T. forsythia aDNA for a complete genome assembly were selected for thorough analyses. We confirmed that the T. forsythia-containing samples have higher amounts of the periodontitis-associated species than the control samples. Despites, other pathogens-derived aDNA was found in the tested samples it was too fragmented and damaged to allow any reasonable reconstruction of these bacteria genomes. The anthropological examination of ancient skulls from which the T. forsythia-containing samples were obtained revealed the pathogenic alveolar bone loss in tooth areas characteristic for advanced periodontitis. Finally, we analyzed the genetic material of ancient T. forsythia strains. As a result, we assembled four ancient T. forsythia genomes - one 2000- and three 1000- year-old. Their comparison with contemporary T. forsythia genomes revealed a lower genetic diversity within the four ancient strains than within contemporary strains. We also investigated the genes of T. forsythia virulence factors and found that several of them (KLIKK protease and bspA genes) differ significantly between ancient and modern bacteria. CONCLUSIONS: In summary, we showed that NGS screening of the ancient human microbiome is a valid approach for the identification of disease-associated microbes. Following this protocol, we provided a new set of information on the emergence, evolution and virulence factors of T. forsythia, the member of the oral dysbiotic microbiome.