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Periodontology 2000 Jun 2022In the initiation or exacerbation of Alzheimer disease, the dissemination of oral microorganisms into the brain tissue or the low-level systemic inflammation have been... (Review)
Review
In the initiation or exacerbation of Alzheimer disease, the dissemination of oral microorganisms into the brain tissue or the low-level systemic inflammation have been speculated to play a role. However, the impact of oral microorganisms, such as Porphyromonas gingivalis, on the pathogenesis of Alzheimer disease and the potential causative relationship is still unclear. The present review has critically reviewed the literature by examining the following aspects: (a) the oral microbiome and the immune response in the elderly population, (b) human studies on the association between periodontal and gut microorganisms and Alzheimer disease, (c) animal and in vitro studies on microorganisms and Alzheimer disease, and (d) preventive and therapeutic approaches. Factors contributing to microbial dysbiosis seem to be aging, local inflammation, systemic diseases, wearing of dentures, living in nursing homes and no access to adequate oral hygiene measures. Porphyromonas gingivalis was detectable in post-mortem brain samples. Microbiome analyses of saliva samples or oral biofilms showed a decreased microbial diversity and a different composition in Alzheimer disease compared to cognitively healthy subjects. Many in-vitro and animal studies underline the potential of P gingivalis to induce Alzheimer disease-related alterations. In animal models, recurring applications of P gingivalis or its components increased pro-inflammatory mediators and β-amyloid in the brain and deteriorated the animals' cognitive performance. Since periodontitis is the result of a disturbed microbial homoeostasis, an effect of periodontal therapy on the oral microbiome and host response related to cognitive parameters may be suggested and should be elucidated in further clinical trials.
Topics: Aged; Alzheimer Disease; Animals; Dysbiosis; Humans; Inflammation; Microbiota; Porphyromonas gingivalis
PubMed: 35244967
DOI: 10.1111/prd.12429 -
Archives of Razi Institute Oct 2022Chronic periodontitis is an inflammatory disease of the dental plaque and affects the soft tissues supporting the tooth. It is one of the most practical oral health... (Review)
Review
Chronic periodontitis is an inflammatory disease of the dental plaque and affects the soft tissues supporting the tooth. It is one of the most practical oral health issues across the globe and adversely affects the quality of life. In a neutrophil-mediated action, the inflammatory response to periodontitis destroys the periodontal ligaments, gums, the alveolar bone, and the cementum. Some of the most associated invasive pathogens with periodontitis are , , and . Google Scholar and PubMed were used to search the evidence using key terms like 'periodontitis,' ',' 'Oral Dysbiosis and Periodontitis,' ' and Periodontitis,' etc. Only studies were included reviewing the and its role in periodontitis. It has been observed from several oral pathogens that has received immense attention due to a strong association between and periodontal disease. also disrupts the delicate balance between various members of the oral microbial communities and promotes oral dysbiosis. The dysbiotic state of the oral microbiome is distinct in functional capabilities and shows a higher expression of genes involved in lipopolysaccharide synthesis, energy regulation, and bacterial motility. Certain virulence factors such as gingipains, LPS, and fimbriae also increase the invasion and pathogenicity of . Its presence in the periodontal tissues increases the secretion of numerous pro-inflammatory mediators such as TNF-α, IL-8, and IL-1β, leading to the destruction of soft gingival tissues and ligaments. Early detection of periodontitis and immediate treatment can prevent soft tissue destruction and dentition loss. In conclusion, details about the oral microbiome, oral dysbiosis, and inflammation may offer new therapeutic options in the future, including a personalized approach and the use of combination therapy.
Topics: Dysbiosis; Inflammation; Periodontitis; Porphyromonas gingivalis; Quality of Life; Humans
PubMed: 37123122
DOI: 10.22092/ARI.2021.356596.1875 -
Frontiers in Cellular and Infection... 2020Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a... (Review)
Review
Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a variety of systemic system diseases such as cancer, cardiovascular disease, diabetes, rheumatoid arthritis, non-alcoholic fatty liver, and Alzheimer's disease. () is the most important pathogenic bacteria for periodontal disease. It can produce outer membrane vesicles (OMVs) and release them into the environment, playing an important role in its pathogenesis. This article focuses on OMVs, reviews its production and regulation, virulence components, mode of action and related diseases, with a view to providing new ideas for the prevention and treatment of diseases related to infections.
Topics: Humans; Periodontal Diseases; Porphyromonas gingivalis; Virulence; Virulence Factors
PubMed: 33585266
DOI: 10.3389/fcimb.2020.585917 -
Journal of Dental Research May 2023Gingival fibroblasts (GFs) are essential components of the periodontium, which are responsible for the maintenance of tissue structure and integrity. However, the... (Review)
Review
Gingival fibroblasts (GFs) are essential components of the periodontium, which are responsible for the maintenance of tissue structure and integrity. However, the physiological role of GFs is not restricted to the production and remodeling of the extracellular matrix. GFs also act as sentinel cells that modulate the immune response to oral pathogens invading the gingival tissue. As an important "nonclassical" component of the innate immune system, GFs respond to bacteria and damage-related signals by producing cytokines, chemokines, and other inflammatory mediators. Although the activation of GFs supports the elimination of invading bacteria and the resolution of inflammation, their uncontrolled or excessive activation may promote inflammation and bone destruction. This occurs in periodontitis, a chronic inflammatory disease of the periodontium initiated and sustained by dysbiosis. In the inflamed gingival tissue, GFs acquire imprinted proinflammatory phenotypes that promote the growth of inflammophilic pathogens, stimulate osteoclastogenesis, and contribute to the chronicity of inflammation. In this review, we discuss the biological functions of GFs in healthy and inflamed gingival tissue, highlighting recent studies that provide insight into their role in the pathogenesis of periodontal diseases. We also draw parallels with the recently discovered fibroblast populations identified in other tissues and their roles in health and disease. This knowledge should be used in future studies to discover more about the role of GFs in periodontal diseases, especially chronic periodontitis, and to identify therapeutic strategies targeting their pathological interactions with oral pathogens and the immune system.
Topics: Humans; Porphyromonas gingivalis; Inflammation; Gingiva; Chronic Periodontitis; Fibroblasts
PubMed: 36883660
DOI: 10.1177/00220345231151921 -
Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion.Nature Communications Sep 2021Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and...
Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into Apc mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between Porphyromonas species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence.
Topics: Bacteria; Butyrates; Carcinogenesis; Cellular Senescence; Colorectal Neoplasms; Epithelial Cells; Feces; Gastrointestinal Microbiome; Humans; Intestines; Porphyromonas; RNA, Ribosomal, 16S
PubMed: 34584098
DOI: 10.1038/s41467-021-25965-x -
International Journal of Oral Science Sep 2021Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a...
Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.
Topics: Animals; Colitis, Ulcerative; Mice; Mice, Inbred C57BL; Porphyromonas gingivalis; Protein-Arginine Deiminases; Virulence Factors
PubMed: 34593756
DOI: 10.1038/s41368-021-00136-2 -
Frontiers in Cellular and Infection... 2022(Pg), the keystone pathogen in chronic periodontitis, is reported to initiate Alzheimer's disease pathologies in preclinical studies. However, the specific mechanisms...
BACKGROUND
(Pg), the keystone pathogen in chronic periodontitis, is reported to initiate Alzheimer's disease pathologies in preclinical studies. However, the specific mechanisms and signaling pathways acting on the brain still need to be further explored. Outer membrane vesicles are derived from Gram-negative bacteria and contain many virulence factors of bacteria. We hypothesized that outer membrane vesicles are an important weapon of to initiate Alzheimer's disease pathologies.
METHODS
The outer membrane vesicles of (Pg OMVs, 4 mg/kg) or saline were delivered to 14-month-old mice by oral gavage every other day for eight weeks. Behavioral alterations were assessed by the open field test, Morris water maze, and Y-maze test. Blood-brain barrier permeability, neuroinflammation, tau phosphorylation, and NLRP3 inflammasome-related protein were analyzed.
RESULTS
Pg OMVs impaired memory and learning ability of mice and decreased tight junction-related gene expression ZO-1, occludin, claudin-5, and occludin protein expression in the hippocampus. Pg OMVs could be detected in the hippocampus and cortex three days after oral gavage. Furthermore, Pg OMVs activated both astrocytes and microglia and elevated IL-1β, tau phosphorylation on the Thr231 site, and NLRP3 inflammasome-related protein expression in the hippocampus. In studies, Pg OMV (5 µg/ml) stimulation increased the mRNA and immunofluorescence of NLRP3 in BV2 microglia, which were significantly inhibited by the NLRP3 inhibitor MCC950. In contrast, the tau phosphorylation in N2a neurons was enhanced after treatment with conditioned media from Pg OMV-stimulated microglia, which was attenuated after pretreatment with MCC950.
CONCLUSIONS
These results indicate that Pg OMVs prompt memory dysfunction, neuroinflammation, and tau phosphorylation and trigger NLRP3 inflammasome in the brain of middle-aged mice. We propose that Pg OMVs play an important role in activating neuroinflammation in the AD-like pathology triggered by , and NLRP3 inflammasome activation is a possible mechanism.
Topics: Alzheimer Disease; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Neuroinflammatory Diseases; Occludin; Phosphorylation; Porphyromonas gingivalis; tau Proteins
PubMed: 36017373
DOI: 10.3389/fcimb.2022.925435 -
International Journal of Oral Science Sep 2021Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, has been shown to accelerate the progression of atherosclerosis (AS). However, the definite...
Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, has been shown to accelerate the progression of atherosclerosis (AS). However, the definite mechanisms remain elusive. Emerging evidence supports an association between mitochondrial dysfunction and AS. In our study, the impact of P. gingivalis on mitochondrial dysfunction and the potential mechanism were investigated. The mitochondrial morphology of EA.hy926 cells infected with P. gingivalis was assessed by transmission electron microscopy, mitochondrial staining, and quantitative analysis of the mitochondrial network. Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP) levels. Cellular ATP production was examined by a luminescence assay kit. The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence. Mdivi-1, a specific Drp1 inhibitor, was used to elucidate the role of Drp1 in mitochondrial dysfunction. Our findings showed that P. gingivalis infection induced mitochondrial fragmentation, increased the mtROS levels, and decreased the MMP and ATP concentration in vascular endothelial cells. We observed upregulation of Drp1 (Ser616) phosphorylation and translocation of Drp1 to mitochondria. Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P. gingivalis. Collectively, these results revealed that P. gingivalis infection promoted mitochondrial fragmentation and dysfunction, which was dependent on Drp1. Mitochondrial dysfunction may represent the mechanism by which P. gingivalis exacerbates atherosclerotic lesions.
Topics: Endothelial Cells; Mitochondria; Mitochondrial Dynamics; Porphyromonas gingivalis
PubMed: 34475379
DOI: 10.1038/s41368-021-00134-4 -
Frontiers in Cellular and Infection... 2022Autophagy is an immune homeostasis process induced by multiple intracellular and extracellular signals. Inflammation is a protective response to harmful stimuli such as... (Review)
Review
Autophagy is an immune homeostasis process induced by multiple intracellular and extracellular signals. Inflammation is a protective response to harmful stimuli such as pathogen microbial infection and body tissue damage. infection elicits both autophagy and inflammation, and dysregulation of autophagy and inflammation promotes pathology. This review focuses on the interaction between autophagy and inflammation caused by infection, aiming to elaborate on the possible mechanism involved in the interaction.
Topics: Autophagy; Homeostasis; Humans; Inflammation; Porphyromonas gingivalis
PubMed: 35846745
DOI: 10.3389/fcimb.2022.892610 -
Odontology Jan 2022Porphyromonas gingivalis, a Gram-negative anaerobic bacillus present in periodontal disease, is considered one of the major pathogens in periodontitis. A literature... (Review)
Review
Porphyromonas gingivalis, a Gram-negative anaerobic bacillus present in periodontal disease, is considered one of the major pathogens in periodontitis. A literature search for English original studies, case series and review articles published up to December 2019 was performed using the MEDLINE, PubMed and GoogleScholar databases, with the search terms "Porphyromonas gingivalis" AND the potentially associated condition or systemic disease Abstracts and full text articles were used to make a review of published research literature on P. gingivalis outside the oral cavity. The main points of interest of this narrative review were: (i) a potential direct action of the bacterium and not the systemic effects of the inflammatory acute-phase response induced by the periodontitis, (ii) the presence of the bacterium (viable or not) in the organ, or (iii) the presence of its virulence factors. Virulence factors (gingipains, capsule, fimbriae, hemagglutinins, lipopolysaccharide, hemolysin, iron uptake transporters, toxic outer membrane blebs/vesicles, and DNA) associated with P. gingivalis can deregulate certain functions in humans, particularly host immune systems, and cause various local and systemic pathologies. The most recent studies linking P. gingivalis to systemic diseases were discussed, remembering particularly the molecular mechanisms involved in different infections, including cerebral, cardiovascular, pulmonary, bone, digestive and peri-natal infections. Recent involvement of P. gingivalis in neurological diseases has been demonstrated. P. gingivalis modulates cellular homeostasis and increases markers of inflammation. It is also a factor in the oxidative stress involved in beta-amyloid production.
Topics: Adhesins, Bacterial; Gingipain Cysteine Endopeptidases; Humans; Periodontitis; Porphyromonas gingivalis
PubMed: 34410562
DOI: 10.1007/s10266-021-00647-8