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Journal of Periodontology Oct 2020Epidemiological studies have identified an association between periodontitis and Alzheimer disease (AD); however, the nature of this association has been unclear. Recent...
Epidemiological studies have identified an association between periodontitis and Alzheimer disease (AD); however, the nature of this association has been unclear. Recent work suggests that brain colonization by the periodontal pathogen Porphyromonas gingivalis may link these two inflammatory and degenerative conditions. Evidence of P. gingivalis infiltration has been detected in autopsy specimens from the brains of people with AD and in cerebrospinal fluid of individuals diagnosed with AD. Gingipains, a class of P. gingivalis proteases, are found in association with neurons, tau tangles, and beta-amyloid in specimens from the brains of individuals with AD. The brains of mice orally infected with P. gingivalis show evidence of P. gingivalis infiltration, along with various neuropathological hallmarks of AD. Oral administration of gingipain inhibitors to mice with established brain infections decreases the abundance of P. gingivalis DNA in brain and mitigates the neurotoxic effects of P. gingivalis infection. Thus, gingipain inhibition could provide a potential approach to the treatment of both periodontitis and AD.
Topics: Adhesins, Bacterial; Alzheimer Disease; Animals; Bacteroidaceae Infections; Cysteine Endopeptidases; Humans; Mice; Periodontitis; Porphyromonas gingivalis
PubMed: 32533852
DOI: 10.1002/JPER.20-0104 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2022Periodontitis, one of the most common inflammatory oral diseases in human beings, threatens the health of teeth and mouth and is closely associated with the development... (Review)
Review
Periodontitis, one of the most common inflammatory oral diseases in human beings, threatens the health of teeth and mouth and is closely associated with the development of many systemic diseases. Existing research about the pathogenesis of periodontitis mainly focuses on the oral microbial homeostasis and its complex interaction with the immune system. Among all the oral microorganisms, ( ) is considered to be the main pathogen causing chronic periodontitis. Recent studies have shown that poesseses HmuY, a special heme binding protein, which binds with heme to provide essential nutrition for and activates the host immune system. Therefore, HmuY plays an important role in the growth, proliferation, invasion, and pathogenesis of and is a potential virulence factor of the bacteria. Existing studies on HmuY are limited to the host immune response that HmuY triggers, and there are still no conclusive findings on whether HmuY participates in the pathogenesis of periodontitis through other ways, such as influencing periodontal bone metabolism. Herein, we reviewed the latest research findings on the biological characteristics and physiological functions of HmuY and its relationship with chronic periodontitis, so as to provide new ideas for in-depth research and further explorations into the pathogenesis of chronic periodontitis.
Topics: Humans; Porphyromonas gingivalis; Chronic Periodontitis; Face; Nutritional Status
PubMed: 36443060
DOI: 10.12182/20221160208 -
Journal of Dental Research Apr 2021Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely... (Review)
Review
Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely critical tasks in responding to a variety of external stimuli and dangers through the regulation of specific built-in molecular mechanisms in a context-dependent fashion at cellular levels. Gingival epithelial cells form an anatomic architecture that confers defense, robustness, and adaptation toward external aggressions, most critically to colonizing microorganisms, among other functions. Accordingly, recent studies unraveled previously uncharacterized response mechanisms in gingival epithelial cells that are constructed to rapidly exert biocidal effects against invader pathobiotic bacteria, such as , through small danger molecule signaling. The host-adapted bacteria, however, have developed adroit strategies to 1) exploit the epithelia as privileged growth niches and 2) chronically target cellular bactericidal and homeostatic metabolic pathways for successful bacterial persistence. As the overgrowth of colonizing microorganisms in the gingival mucosa can shift from homeostasis to dysbiosis or a diseased state, it is crucial to understand how the innate modulatory molecules are intricately involved in antibacterial pathways and how they shape susceptibility versus resistance in the epithelium toward pathogens. Thus, in this review, we highlight recent discoveries in gingival epithelial cell research in the context of bacterial colonizers. The current knowledge outlined here demonstrates the ability of epithelial cells to possess highly organized defense machineries, which can jointly regulate host-derived danger molecule signaling and integrate specific global responses against opportunistic bacteria to combat microbial incursion and maintain host homeostatic balance. These novel examples collectively suggest that the oral epithelia are equipped with a dynamically robust and interconnected defense system encompassing sensors and various effector molecules that arrange and achieve a fine-tuned and advanced response to diverse bacteria.
Topics: Epithelial Cells; Gingiva; Homeostasis; Mouth Mucosa; Porphyromonas gingivalis
PubMed: 33203318
DOI: 10.1177/0022034520973012 -
Reumatologia Clinica Mar 2023Periodontitis and rheumatoid arthritis (RA) have been associated in a bidirectional way. The objective of this study was to determine the association between clinical...
BACKGROUND AND OBJECTIVE
Periodontitis and rheumatoid arthritis (RA) have been associated in a bidirectional way. The objective of this study was to determine the association between clinical parameters of periodontitis and RA.
MATERIALS AND METHODS
Seventy-five (75) participants distributed in 3 groups (21 patients with periodontitis without RA, 33 patients with periodontitis with RA and 21 patients with reduced periodontium with RA) were included in this cross-sectional study. A full periodontal and medical examination was performed in each patient. Additionally, subgingival plaque samples for the detection of Porphyromonas gingivalis (P. gingivalis) and blood samples for biochemical markers of RA were also taken. Logistic regression analysis adjusted for confounding variables, Spearman's rank correlation coefficient and a linear multivariate regression were used to analyze the data.
RESULTS
Patients with RA presented less severity of periodontal parameters. The highest levels of anti-citrullinated protein antibodies were detected in non-periodontitis patients with RA. Covariates such as age, P. gingivalis, diabetes, smoking, osteoporosis and use of medication were not associated with RA. All periodontal variables and P. gingivalis expressed a negative correlation with biochemical markers of RA (P<0.05).
CONCLUSIONS
Periodontitis was not associated with RA. Furthermore, there was no correlation between periodontal clinical parameters and biochemical markers of RA.
Topics: Humans; Cross-Sectional Studies; Arthritis, Rheumatoid; Periodontitis; Porphyromonas gingivalis; Biomarkers
PubMed: 36906387
DOI: 10.1016/j.reumae.2022.03.006 -
International Journal of Environmental... Sep 2021A particular role for (Pg) and (Aa) has been suggested in periodontitis and rheumatoid arthritis (RA), as these bacteria could initiate the formation of rheumatoid...
A particular role for (Pg) and (Aa) has been suggested in periodontitis and rheumatoid arthritis (RA), as these bacteria could initiate the formation of rheumatoid factor (RF) and anticitrullinated protein autoantibodies (ACPA). We assessed whether serum antibodies against Pg and Aa in RA patients and non-RA controls reflect the subgingival presence of Pg and Aa, and evaluated the relationship of these antibodies to the severity of periodontal inflammation and RA-specific serum autoantibodies. In 70 Indonesian RA patients and 70 non-RA controls, the subgingival presence of Pg and Aa was assessed by bacterial 16S rRNA gene sequencing, and serum IgG levels specific for Pg and Aa were determined. In parallel, serum levels of ACPA (ACPA:IgG,IgA) and RF (RF:IgM,IgA) were measured. The extent of periodontal inflammation was assessed by the periodontal inflamed surface area. In both RA patients and the controls, the presence of subgingival Pg and Aa was comparable, anti-Pg and anti-Aa antibody levels were associated with the subgingival presence of Pg and Aa, and anti-Pg did not correlate with ACPA or RF levels. The subgingival Pg and Aa were not related to RA. No noteworthy correlation was detected between the antibodies against Pg and Aa, and RA-specific autoantibodies.
Topics: Arthritis, Rheumatoid; Autoantibodies; Humans; Porphyromonas gingivalis; RNA, Ribosomal, 16S; Rheumatoid Factor
PubMed: 34574484
DOI: 10.3390/ijerph18189560 -
Frontiers in Cellular and Infection... 2023Periodontitis and inflammatory bowel diseases (IBD) are inflammatory diseases of the gastrointestinal tract that share common features of microbial-induced ecological... (Review)
Review
Periodontitis and inflammatory bowel diseases (IBD) are inflammatory diseases of the gastrointestinal tract that share common features of microbial-induced ecological dysregulation and host immune inflammatory response. The close relationship between periodontitis and IBD is characterized by a higher prevalence of IBD in patients with periodontitis and a higher prevalence and severity of periodontitis in patients with IBD, indicating that periodontitis and IBD are different from the traditional independent diseases and form an "Oral-Gut" axis between the two, which affect each other and thus form a vicious circle. However, the specific mechanisms leading to the association between the two are not fully understood. In this article, we describe the interconnection between periodontitis and IBD in terms of microbial pathogenesis and immune dysregulation, including the ectopic colonization of the gut by pathogenic bacteria associated with periodontitis that promotes inflammation in the gut by activating the host immune response, and the alteration of the oral microbiota due to IBD that affects the periodontal inflammatory response. Among the microbial factors, pathogenic bacteria such as , and may act as the microbial bridge between periodontitis and IBD, while among the immune mechanisms, Th17 cell responses and the secreted pro-inflammatory factors IL-1β, IL-6 and TNF-α play a key role in the development of both diseases. This suggests that in future studies, we can look for targets in the "Oral-Gut" axis to control and intervene in periodontal inflammation by regulating periodontal or intestinal flora through immunological methods.
Topics: Humans; Inflammatory Bowel Diseases; Periodontitis; Inflammation; Porphyromonas gingivalis
PubMed: 36923589
DOI: 10.3389/fcimb.2023.1132420 -
Microbiology and Molecular Biology... Feb 2020is an oral pathogen involved in the widespread disease periodontitis. In recent years, however, this bacterium has been implicated in the etiology of another common... (Review)
Review
is an oral pathogen involved in the widespread disease periodontitis. In recent years, however, this bacterium has been implicated in the etiology of another common disorder, the autoimmune disease rheumatoid arthritis. Periodontitis and rheumatoid arthritis were known to correlate for decades, but only recently a possible molecular connection underlying this association has been unveiled. possesses an enzyme that citrullinates certain host proteins and, potentially, elicits autoimmune antibodies against such citrullinated proteins. These autoantibodies are highly specific for rheumatoid arthritis and have been purported both as a symptom and a potential cause of the disease. The citrullinating enzyme and other major virulence factors of , including some that were implicated in the etiology of rheumatoid arthritis, are targeted to the host tissue as secreted or outer-membrane-bound proteins. These targeting events play pivotal roles in the interactions between the pathogen and its human host. Accordingly, the overall protein sorting and secretion events in are of prime relevance for understanding its full disease-causing potential and for developing preventive and therapeutic approaches. The aim of this review is therefore to offer a comprehensive overview of the subcellular and extracellular localization of all proteins in three reference strains and four clinical isolates of , as well as the mechanisms employed to reach these destinations.
Topics: Arthritis, Rheumatoid; Autoantibodies; Citrullination; Host-Pathogen Interactions; Humans; Mouth; Periodontitis; Porphyromonas gingivalis; Protein Transport; Virulence Factors
PubMed: 31896547
DOI: 10.1128/MMBR.00032-19 -
Medicine Oct 2022We previously reported that oral herpesviruses, such as Epstein-Barr virus (EBV), are associated with periodontitis. However, the relationship between oral EBV or dual...
We previously reported that oral herpesviruses, such as Epstein-Barr virus (EBV), are associated with periodontitis. However, the relationship between oral EBV or dual oral EBV and Porphyromonas gingivalis infections and periodontal inflammation severity remains unclear. We conducted this study to determine the relationship between oral EBV and P gingivalis prevalence and the periodontal inflamed surface area (PISA) in middle-aged and older adults. We analyzed 205 patients (median age, 70 years) who visited Hiroshima University Hospital. Tongue swab samples were used to investigate the presence of EBV and P gingivalis DNA using real-time PCR. Probing pocket depth and bleeding on probing were measured at 6 sites per tooth. PISA scores were calculated based on the results of probing pocket depth and bleeding on probing. Propensity scores were calculated via logistic regression analysis of 8 clinical factors: age, sex, smoking status, remaining teeth, denture use, hypertension, diabetes, and hyperlipidemia. EBV DNA was present in 41 of the 205 participants (20.0%). Thirty-seven EBV-positive or -negative participants in 74 matched pairs after propensity-score matching were examined via univariate analysis. EBV-positive participants exhibited higher plaque control record scores and PISAs than did EBV-negative participants. EBV DNA was significantly associated with plaque control record scores and PISA (both P = .04). Of the 205 participants, 111 were positive for P gingivalis (54.1%). Nineteen participants (9.3%) were infected with both oral EBV and P gingivalis. Logistic regression analysis revealed that dual infection with EBV and P gingivalis was significantly associated with diabetes (odds ratio = 3.37, 95% confidence interval: 1.13-10.1; P = .03). Oral EBV prevalence is associated with oral hygiene and the spread of inflamed periodontal tissue. Diabetes may be a risk factor for dual infection with oral EBV and P gingivalis.
Topics: Middle Aged; Humans; Aged; Herpesvirus 4, Human; Porphyromonas gingivalis; Epstein-Barr Virus Infections; Cross-Sectional Studies; Prevalence; DNA
PubMed: 36316924
DOI: 10.1097/MD.0000000000031282 -
Virulence Dec 2022To investigate the role of adrenergic signalling (AS) in the host immune response and virulence, we compared norepinephrine (NE) and isoproterenol (ISO) responses in ....
To investigate the role of adrenergic signalling (AS) in the host immune response and virulence, we compared norepinephrine (NE) and isoproterenol (ISO) responses in . infection was evaluated by survival; humoral immune responses (i.e. melanization and and mRNA expression); cellular immune responses (i.e. haemocyte count, nodulation by histology); and recovery (CFU/mL). was cultivated in the presence of ISO (PgISO) or NE and injected into the larvae for survival evaluation. Finally, we co-injected ISO and PgISO to evaluate the concomitant effects on the immune response and bacterial virulence. None of the ligands were toxic to the larvae; ISO increased haemocyte number, even after infection, by mobilizing sessile haemocytes in a β-adrenergic-specific manner, while NE showed the opposite effect. ISO treatment reduced larval mortality and the number of recovered bacteria, while NE increased mortality and showed no effect on bacterial recovery. ISO and NE had similar effects on melanization and decreased the expression of cecropin. Although co-cultivation with NE and ISO increased the gene expression of bacterial virulence factors , only the injection of PgISO increased larval death, which was partially reversed by circulating ISO. Therefore, α- and β-adrenergic signalling had opposite effects after infection. Ultimately, the catecholamine influence on the immune response overcame the effect of more virulent strains. The effect of AS directly on the pathogen found did not translate to the setting.
Topics: Adrenergic Agents; Animals; Cecropins; Immunity, Innate; Isoproterenol; Larva; Moths; Norepinephrine; Porphyromonas gingivalis; RNA, Messenger; Virulence; Virulence Factors
PubMed: 36121102
DOI: 10.1080/21505594.2022.2123302 -
International Journal of Molecular... Apr 2024(Pg) and its gingipain proteases contribute to Alzheimer's disease (AD) pathogenesis through yet unclear mechanisms. Cellular secretion of small extracellular vesicles...
(Pg) and its gingipain proteases contribute to Alzheimer's disease (AD) pathogenesis through yet unclear mechanisms. Cellular secretion of small extracellular vesicles or exosomes (EXO) increases with aging as part of the senescence-associated secretory phenotype (SASP). We have shown that EXO isolated from Pg-infected dendritic cells contain gingipains and other Pg antigens and transmit senescence to bystander gingival cells, inducing alveolar bone loss in mice in vivo. Here, EXO were isolated from the gingiva of mice and humans with/without periodontitis (PD) to determine their ability to penetrate the blood-brain barrier (BBB) in vitro and in vivo. PD was induced by Pg oral gavage for 6 weeks in C57B6 mice. EXO isolated from the gingiva or brain of donor Pg-infected (PD EXO) or control animals (Con EXO) were characterized by NTA, Western blot, and TEM. Gingival PD EXO or Con EXO were labeled and injected into the gingiva of uninfected WT mouse model. EXO biodistribution in brains was tracked by an in vivo imaging system (IVIS) and confocal microscopy. The effect of human PD EXO on BBB integrity and permeability was examined using TEER and FITC dextran assays in a human in vitro 3D model of the BBB. Pg antigens (RGP and Mfa-1) were detected in EXO derived from gingival and brain tissues of donor Pg-infected mice. Orally injected PD EXO from donor mice penetrated the brains of recipient uninfected mice and colocalized with hippocampal microglial cells. IL-1β and IL-6 were expressed in human PD EXO and not in Con EXO. Human PD EXO promoted BBB permeability and penetrated the BBB in vitro. This is the first demonstration that microbial-induced EXO in the oral cavity can disseminate, cross the BBB, and may contribute to AD pathogenesis.
Topics: Blood-Brain Barrier; Animals; Humans; Mice; Extracellular Vesicles; Porphyromonas gingivalis; Periodontitis; Gingiva; Mice, Inbred C57BL; Male; Exosomes; Female; Bacteroidaceae Infections
PubMed: 38674094
DOI: 10.3390/ijms25084509