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Clinical and Experimental Dental... Apr 2023This review was conducted to assess the effectiveness of xylitol against Porphyromonas gingivalis anaerobic species, a key microbe contributing to periodontal disease... (Review)
Review
OBJECTIVE
This review was conducted to assess the effectiveness of xylitol against Porphyromonas gingivalis anaerobic species, a key microbe contributing to periodontal disease pathogenesis.
MATERIAL AND METHODS
Relevant studies published on seven online databases (Cochrane, Ovid, Pubmed, Pubmed Central, Scopus, Google Scholar, and Web of Science) were included in accordance with the PRISMA guidelines. Inclusion criteria allowed all study designs involving xylitol and P. gingivalis, literature published since the year 2000, and all xylitol delivery forms.
RESULTS
The initial search yielded 186 papers. After the removal of duplicates, five reviewers screened every article for eligibility and seven articles were selected for data extraction. Four out of seven included studies assessed the dose-dependent effect of xylitol on P. gingivalis growth, two studies assessed the effect of xylitol on P. gingivalis-induced cytokine expression, and one study assessed both domains.
CONCLUSIONS
From the in vitro studies included in this systematic review, there is some evidence of xylitol's inhibitory effect on P. gingivalis. However, more evidence derived from in vivo studies is required to confirm its effectiveness warranting their routine use.
Topics: Humans; Porphyromonas gingivalis; Xylitol; Periodontal Diseases; Cytokines
PubMed: 36894516
DOI: 10.1002/cre2.724 -
Frontiers in Immunology 2023Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to () and RA has been...
BACKGROUND
Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to () and RA has been established, but data on saliva antibodies to in RA are lacking. We evaluated antibodies to in serum and saliva in two Swedish RA studies as well as their association with RA, periodontitis, antibodies to citrullinated proteins (ACPA), and RA disease activity.
METHODS
The SARA (secretory antibodies in RA) study includes 196 patients with RA and 101 healthy controls. The Karlskrona RA study includes 132 patients with RA ≥ 61 years of age, who underwent dental examination. Serum Immunoglobulin G (IgG) and Immunoglobulin A (IgA) antibodies and saliva IgA antibodies to the -specific Arg-specific gingipain B (RgpB) were measured in patients with RA and controls.
RESULTS
The level of saliva IgA anti-RgpB antibodies was significantly higher among patients with RA than among healthy controls in multivariate analysis adjusted for age, gender, smoking, and IgG ACPA (p = 0.022). Saliva IgA anti-RgpB antibodies were associated with RA disease activity in multivariate analysis (p = 0.036). Anti-RgpB antibodies were not associated with periodontitis or serum IgG ACPA.
CONCLUSION
Patients with RA had higher levels of saliva IgA anti-RgpB antibodies than healthy controls. Saliva IgA anti-RgpB antibodies may be associated with RA disease activity but were not associated with periodontitis or serum IgG ACPA. Our results indicate a local production of IgA anti-RgpB in the salivary glands that is not accompanied by systemic antibody production.
Topics: Humans; Sweden; Porphyromonas gingivalis; Saliva; Peptides, Cyclic; Arthritis, Rheumatoid; Immunoglobulin G; Gingipain Cysteine Endopeptidases; Periodontitis; Immunoglobulin A
PubMed: 37325636
DOI: 10.3389/fimmu.2023.1183194 -
Frontiers in Cellular and Infection... 2023is a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. expresses a variety of virulence factors that disrupt innate... (Review)
Review
is a Gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. expresses a variety of virulence factors that disrupt innate and adaptive immunity, allowing to survive and multiply in the host and destroy periodontal tissue. In addition to periodontal disease, is also associated with systemic diseases, of which insulin resistance is an important pathological basis. causes a systemic inflammatory response, disrupts insulin signaling pathways, induces pancreatic β-cell hypofunction and reduced numbers, and causes decreased insulin sensitivity leading to insulin resistance (IR). In this paper, we systematically review the studies on the mechanism of insulin resistance induced by , discuss the association between and systemic diseases based on insulin resistance, and finally propose relevant therapeutic approaches. Overall, through a systematic review of the mechanisms related to systemic diseases caused by through insulin resistance, we hope to provide new insights for future basic research and clinical interventions for related systemic diseases.
Topics: Humans; Porphyromonas gingivalis; Insulin Resistance; Base Composition; RNA, Ribosomal, 16S; Phylogeny; Sequence Analysis, DNA; Insulin
PubMed: 37520442
DOI: 10.3389/fcimb.2023.1209381 -
Trends in Microbiology Jan 2021Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of... (Review)
Review
Proteases are critical virulence determinants of Porphyromonas gingivalis, an emerging Alzheimer's disease, cancer, and arthritis pathogen and established agent of periodontitis. Transposon sequencing has been employed to define the core essential genome of this bacterium and genes conditionally essential in multiple environments - abscess formation; epithelial colonization; and cigarette smoke toxin exposure; as well as to elucidate genes required for iron acquisition and a functional type 9 secretion system. Validated and predicted protein catabolism genes identified include a combination of established virulence factors and a larger set of seemingly more mundane proteolytic genes. The functions and relevance of genes that share essentiality in multiple disease-relevant conditions are examined. These common stress-related genes may represent particularly attractive therapeutic targets for the control of P. gingivalis infections.
Topics: Animals; Bacterial Proteins; Bacteroidaceae Infections; Genes, Essential; Humans; Porphyromonas gingivalis; Virulence Factors
PubMed: 33071035
DOI: 10.1016/j.tim.2020.09.002 -
Frontiers in Immunology 2022() is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. has recently been detected in rheumatoid... (Review)
Review
() is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. has recently been detected in rheumatoid arthritis (RA), cardiovascular disease, and tumors, as well as Alzheimer's disease (AD), and the presence of in these diseases are correlated with poor prognosis. Macrophages are major innate immune cells which modulate immune responses against pathogens, however, multiple bacteria have evolved abilities to evade or even subvert the macrophages' immune response, in which subsequently promote the diseases' initiation and progression. as a keystone pathogen of periodontitis has received increasing attention for the onset and development of systemic diseases. induces macrophage polarization and inflammasome activation. It also causes immune response evasion which plays important roles in promoting inflammatory diseases, autoimmune diseases, and tumor development. In this review, we summarize recent discoveries on the interaction of and macrophages in relevant disease development and progression, such as periodontitis, atherosclerosis, RA, AD, and cancers, aiming to provide an in-depth mechanistic understanding of this interaction and potential therapeutic strategies.
Topics: Arthritis, Rheumatoid; Humans; Inflammasomes; Macrophage Activation; Macrophages; Periodontitis; Porphyromonas gingivalis
PubMed: 35967399
DOI: 10.3389/fimmu.2022.952040 -
Vaccine Jul 2023Periodontal disease has become a serious public health problem, not only causing tooth loss, but also inducing chronic disorders of extra-oral organs. The present study...
Periodontal disease has become a serious public health problem, not only causing tooth loss, but also inducing chronic disorders of extra-oral organs. The present study assessed an intranasal vaccine strategy to prevent periodontal disease using outer membrane vesicles (OMVs) of two major periodontopathic bacteria, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa). We compared the morphology, composition, and immune activity between OMVs of Pg strain ATCC 33277 and Aa strain Y4. Aa OMVs had a smoother surface and stronger lipid A activity compared to Pg OMVs. The in vitro immune activity elicited by Aa OMVs in macrophage-like cells was remarkably stronger than that of Pg OMVs. Intranasal immunization of mice with Aa OMVs alone resulted in robust, humoral immune responses in blood and saliva. Despites the intrinsically low mucosal immunogenicity of Pg OMVs alone, using Aa OMVs as a mucosal adjuvant strongly enhanced Pg-specific immune responses, resulting in both serum IgG and salivary IgA, both of which aggregated Pg and Aa cells. Furthermore, Aa OMVs were found to be a more potent mucosal adjuvant than Poly(I:C) in the context of enhancing the production of Pg-specific IgG (especially IgG2a) and IgA. In addition, in a randomized, blinded study, mice oral challenged with Pg and Aa after intranasal immunization with Pg OMVs and Aa OMVs had significantly decreased numbers of both microorganisms compared to mock-immunized mice. Furthermore, in an intracerebral injection mouse model, there were no serious adverse effects on the brain even after administrating a dose of OMVs as same as that used for intranasal administration. Taken together, the bivalent OMV intranasal vaccine may be effective in preventing colonization of periodontopathic bacteria in the oral cavity and related systemic disorders associated with periodontal diseases.
Topics: Mice; Animals; Administration, Intranasal; Vaccines, Combined; Periodontal Diseases; Porphyromonas gingivalis; Adjuvants, Immunologic; Immunoglobulin G; Immunoglobulin A; Antibodies, Bacterial
PubMed: 37302966
DOI: 10.1016/j.vaccine.2023.05.058 -
Journal of Integrative Neuroscience Aug 2023Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis...
BACKGROUND
Periodontitis is one of the most common chronic inflammatory disorders in adults. Although clinical studies have suggested a causal relationship between periodontitis and major depression (MD), the biological mechanisms by which periodontitis instigates MD are unknown. We investigated whether a systemic administration of lipopolysaccharide (LPS) from (), a major Gram-negative pathogen of periodontitis, causes depressive-like behavior and glial activation in the hippocampus and the prefrontal cortex (PFC), which are MD-related brain regions.
MATERIALS AND METHODS
Eight-week-old male Sprague Dawley rats were randomly divided into a behavioral test group and an immunohistochemistry group. The rats in each group were further assigned to the sham injection (saline) and -lipopolysaccharide (-LPS) injection protocols. The rats received an intraperitoneal injection of saline or -LPS with gradually increasing doses (day 1: 0.5, day 2: 0.5, day 3: 0.75, day 4: 0.75, day 5: 1.0, day 6: 1.0, and day 7: 1.0 mg/kg of body weight) for seven consecutive days. After the systemic administration, the behavior test group underwent the forced swimming test (FST) and Y-maze test. For the immunohistochemistry group, we quantified the immunoreactivity for microglial Iba-1 (ionized calcium-binding adapter molecule 1) and astrocytic glial fibrillary acidic protein (GFAP) in the hippocampus (dentate gyrus [DG], cornu ammonis [CA1 and CA3]) and PFC (prelimbic [PrL] and the infralimbic [IL]) areas.
RESULTS
The FST immobility time in the -LPS group was significantly longer than that in the sham group. In the Y-maze test, a significant decline in spontaneous alternation behavior was observed in the -LPS group compared to the sham group. The peripheral administration of -LPS significantly increased the immunoreactivity for Iba-1 in the CA3 and PrL. -LPS injection significantly increased the immunoreactivity for GFAP in the DG, CA1, and CA3.
CONCLUSIONS
The major result of this study is that a repeated systemic administration of -LPS caused depressive-like behavior and both microglial and astrocytic activation in rats. This finding may comprise biological evidence of a causal relationship between periodontitis and MD.
Topics: Male; Rats; Animals; Rats, Sprague-Dawley; Lipopolysaccharides; Porphyromonas gingivalis; Depressive Disorder, Major; Hippocampus
PubMed: 37735127
DOI: 10.31083/j.jin2205120 -
Periodontology 2000 Jun 2022Extensive research in humans and animal models has begun to unravel the complex mechanisms that drive the immunopathogenesis of periodontitis. Neutrophils mount an early... (Review)
Review
Extensive research in humans and animal models has begun to unravel the complex mechanisms that drive the immunopathogenesis of periodontitis. Neutrophils mount an early and rapid response to the subgingival oral microbiome, producing destructive enzymes to kill microbes. Chemokines and cytokines are released that attract macrophages, dendritic cells, and T cells to the site. Dendritic cells, the focus of this review, are professional antigen-presenting cells on the front line of immune surveillance. Dendritic cells consist of multiple subsets that reside in the epithelium, connective tissues, and major organs. Our work in humans and mice established that myeloid dendritic cells are mobilized in periodontitis. This occurs in lymphoid and nonlymphoid oral tissues, in the bloodstream, and in response to Porphyromonas gingivalis. Moreover, the dendritic cells mature in situ in gingival lamina propria, forming immune conjugates with cluster of differentiation (CD) 4+ T cells, called oral lymphoid foci. At such foci, the decisions are made as to whether to promote bone destructive T helper 17 or bone-sparing regulatory T cell responses. Interestingly, dendritic cells lack potent enzymes and reactive oxygen species needed to kill and degrade endocytosed microbes. The keystone pathogen P. gingivalis exploits this vulnerability by invading dendritic cells in the tissues and peripheral blood using its distinct fimbrial adhesins. This promotes pathogen dissemination and inflammatory disease at distant sites, such as atherosclerotic plaques. Interestingly, our recent studies indicate that such P. gingivalis-infected dendritic cells release nanosized extracellular vesicles called exosomes, in higher numbers than uninfected dendritic cells do. Secreted exosomes and inflammasome-related cytokines are a key feature of the senescence-associated secretory phenotype. Exosomes communicate in paracrine with neighboring stromal cells and immune cells to promote and amplify cellular senescence. We have shown that dendritic cell-derived exosomes can be custom tailored to target and reprogram specific immune cells responsible for inflammatory bone loss in mice. The long-term goal of these immunotherapeutic approaches, ongoing in our laboratory and others, is to promote human health and longevity.
Topics: Alveolar Bone Loss; Animals; Cytokines; Dendritic Cells; Disease Susceptibility; Humans; Immunotherapy; Mice; Periodontitis; Porphyromonas gingivalis
PubMed: 35244951
DOI: 10.1111/prd.12428 -
Molecular Oral Microbiology Apr 2021Periodontitis is an irreversible, chronic inflammatory disease where inflammophilic pathogenic microbial communities accumulate in the gingival crevice. Neutrophils are... (Review)
Review
Periodontitis is an irreversible, chronic inflammatory disease where inflammophilic pathogenic microbial communities accumulate in the gingival crevice. Neutrophils are a major component of the innate host response against bacterial challenge, and under homeostatic conditions, their microbicidal functions typically protect the host against periodontitis. However, a number of periodontal pathogens developed survival strategies to evade neutrophil microbicidal functions while promoting inflammation, which provides a source of nutrients for bacterial growth. Research on periodontal pathogens has largely focused on a few established species: Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis. However, advances in culture-independent techniques have facilitated the identification of new bacterial species in periodontal lesions, such as the two Gram-positive anaerobes, Filifactor alocis and Peptoanaerobacter stomatis, whose characterization of pathogenic potential has not been fully described. Additionally, there is not a full understanding of the pathogenic mechanisms used against neutrophils by organisms that are abundant in periodontal lesions. This presents a substantial barrier to the development of new approaches to prevent or ameliorate the disease. In this review, we first summarize the neutrophil functions affected by the established periodontal pathogens listed above, denoting unknown areas that still merit a closer look. Then, we review the literature on neutrophil functions and the emerging periodontal pathogens, F. alocis and P. stomatis, comparing the effects of the emerging microbes to that of established pathogens, and speculate on the contribution of these putative pathogens to the progression of periodontal disease.
Topics: Aggregatibacter actinomycetemcomitans; Clostridiales; Humans; Inflammation; Neutrophils; Porphyromonas gingivalis; Treponema denticola
PubMed: 33128827
DOI: 10.1111/omi.12321 -
Frontiers in Immunology 2022Aging is a gradual and progressive deterioration of integrity across multiple organ systems that negatively affects gingival wound healing. The cellular responses... (Review)
Review
Aging is a gradual and progressive deterioration of integrity across multiple organ systems that negatively affects gingival wound healing. The cellular responses associated with wound healing, such as collagen synthesis, cell migration, proliferation, and collagen contraction, have been shown to be lower in gingival fibroblasts (the most abundant cells from the connective gingival tissue) in aged donors than young donors. Cellular senescence is one of the hallmarks of aging, which is characterized by the acquisition of a senescence-associated secretory phenotype that is characterized by the release of pro-inflammatory cytokines, chemokines, growth factors, and proteases which have been implicated in the recruitment of immune cells such as neutrophils, T cells and monocytes. Moreover, during aging, macrophages show altered acquisition of functional phenotypes in response to the tissue microenvironment. Thus, inflammatory and resolution macrophage-mediated processes are impaired, impacting the progression of periodontal disease. Interestingly, salivary antimicrobial peptides, such as histatins, which are involved in various functions, such as antifungal, bactericidal, enamel-protecting, angiogenesis, and re-epithelization, have been shown to fluctuate with aging. Several studies have associated the presence of , a key pathogen related to periodontitis and apical periodontitis, with the progression of Alzheimer's disease, as well as gut, esophageal, and gastric cancers. Moreover, herpes simplex virus types 1 and 2 have been associated with the severity of periodontal disease, cardiovascular complications, and nervous system-related pathologies. This review encompasses the effects of aging on periodontal tissues, how and HSV infections could favor periodontitis and their relationship with other pathologies.
Topics: Humans; Gingiva; Porphyromonas gingivalis; Periodontium; Periodontitis; Periodontal Diseases
PubMed: 36341447
DOI: 10.3389/fimmu.2022.1044334