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International Endodontic Journal Oct 2023Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is...
AIM
Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is triggered. The aim was to evaluate whether lipopolysaccharide (LPS) from Porphyromonas endodontalis and Porphyromonas gingivalis induced angiogenesis-related effects in vitro via TLR2 and TLR4.
METHODOLOGY
Porphyromonas endodontalis LPS (ATCC 35406 and clinical isolate) was purified with TRIzol, whereas P. gingivalis LPS was obtained commercially. The effects of the different LPS (24 h) in endothelial cell migration were analysed by Transwell assays, following quantification in an optical microscope (40×). The effects of LPS on FAK Y397 phosphorylation were assessed by Western blotting. Angiogenesis in vitro was determined in an endothelial tube formation assay (14 h) in Matrigel in the absence or presence of either LPS. IL-6 and VEGF-A levels were determined in cell supernatants, following 24 h treatment with LPS, and measured in multiplex bead immunoassay. The involvement of TLR2 and TLR4 was assessed with blocking antibodies. The statistical analysis was performed using STATA 12® (StataCorp LP).
RESULTS
The results revealed that P. endodontalis LPS, but not P. gingivalis LPS, stimulated endothelial cell migration. Pre-treatment with anti-TLR2 and anti-TLR4 antibodies prevented P. endodontalis LPS-induced cell migration. P. endodontalis LPS promoted FAK phosphorylation on Y397, as observed by an increased p-FAK/FAK ratio. Both P. gingivalis and P. endodontalis LPS (ATCC 35406) induced endothelial tube formation in a TLR-2 and -4-dependent manner, as shown by using blocking antibodies, however, only TLR2 blocking decreased tube formation induced by P. endodontalis (clinical isolate). Moreover, all LPS induced IL-6 and VEGF-A synthesis in endothelial cells. TLR2 and TLR4 were required for IL-6 induction by P. endodontalis LPS (ATCC 35406), while only TLR4 was involved in IL-6 secretion by the other LPS. Finally, VEGF-A synthesis did not require TLR signalling.
CONCLUSION
Porphyromonas endodontalis and P. gingivalis LPS induced angiogenesis via TLR2 and TLR4. Collectively, these data contribute to understanding the role of LPS from Porphyromonas spp. in angiogenesis and TLR involvement.
Topics: Lipopolysaccharides; Toll-Like Receptor 2; Porphyromonas gingivalis; Porphyromonas endodontalis; Vascular Endothelial Growth Factor A; Endothelial Cells; Antibodies, Blocking; Interleukin-6; Toll-Like Receptor 4
PubMed: 37461231
DOI: 10.1111/iej.13957 -
Journal of Clinical Periodontology Nov 2023The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative...
AIM
The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative effects of oral infection with Porphyromonas gingivalis (PG), the major pathogen for periodontitis, on intestinal microbiota and atherosclerosis.
MATERIALS AND METHODS
ApoE mice were fed a normal chow diet (NC), a Western diet (WD) or a WD with oral PG infection (PG). The PG infection was investigated by placing a total of 10 CFUs of live PG into the oral cavity of each mouse using a feeding needle five times a week for 3 weeks. Atherosclerotic lesions of the aortae were measured, and blood lipoproteins and the expression of molecules related to lipid metabolism in the liver were analysed. We also performed 16S RNA sequencing and a microbiome analysis using faeces.
RESULTS
En face bloc preparation of the aortae showed that the PG group had a 1.7-fold increase in atherosclerotic lesions compared with the WD group (p < .01). Serum analyses showed that oral PG infection induced a significant decrease in high-density lipoprotein (HDL) and triglyceride. Western blots of hepatic tissue lysates revealed that PG infection reduced the expression of scavenger receptor class B type 1 (SR-B1) in the liver by 50%. Faecal microbiota analysis revealed that species richness estimates (Chao1, ACE) decreased immediately after PG infection. PG infection also induced a significant decrease in Shannon diversity and an increase in Simpson's indices in the WD-fed mice. PG infection significantly increased the phyla Actinobacteria and Deferribacteres, along with the species Mucispirillum schaedleri and Lactobacillus gasseri, in the mice. The functional study showed that PG infection increased the expression of proteins that function in carbohydrate and glucose metabolism, including phosphotransferase system (PTS) proteins and the GntR family transcriptional regulator.
CONCLUSIONS
Oral PG infection promotes atherosclerosis and induces significant metabolic changes, including reduced serum HDL and reduced hepatic SR-B1 and ABCA1 expression, as well as changes in intestinal microbiota. Our study suggests that intestinal dysbiosis accompanies periodontitis and could play a role in atherosclerosis.
Topics: Mice; Animals; Porphyromonas gingivalis; Gastrointestinal Microbiome; Dysbiosis; Atherosclerosis; Periodontitis
PubMed: 37621247
DOI: 10.1111/jcpe.13864 -
Clinical & Translational Oncology :... Oct 2023Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related... (Review)
Review
Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related to periodontitis pathogenesis and were found to be abundant in the intestinal mucosa of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. Besides, periodontal infections have been found in a variety of tissues and organs, indicating that periodontitis is not just an inflammation limited to the oral cavity. Considering the possible translocation of pathobiont from the oral cavity to the gastrointestinal (GI) tract, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the relationship between periodontitis and GI malignancies by focusing on the oral/gut axis.
Topics: Humans; Periodontitis; Porphyromonas gingivalis; Inflammation; Gastrointestinal Neoplasms
PubMed: 37036595
DOI: 10.1007/s12094-023-03162-0 -
Journal of Periodontal Research Dec 2021Periodontitis is a chronic inflammatory condition that destroys the tooth-supporting tissues and eventually leads to tooth loss. As one of the most prevalent oral... (Review)
Review
Periodontitis is a chronic inflammatory condition that destroys the tooth-supporting tissues and eventually leads to tooth loss. As one of the most prevalent oral conditions, periodontitis endangers the oral health of 70% of people throughout the world. Periodontitis is also related to various systemic diseases, such as diabetes mellitus, atherosclerosis, and rheumatoid arthritis, which not only has a great impact on population health status and the quality of life but also increases the social burden. Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral anaerobic bacterium that plays a key role in the pathogenesis of periodontitis. Porphyromonas gingivalis can express various of virulence factors to overturn innate and adaptive immunities, which makes P. gingivalis survive and propagate in the host, destroy periodontal tissues, and have connection to systemic diseases. Porphyromonas gingivalis can invade into and survive in host tissues by destructing the gingival epithelial barrier, internalizing into the epithelial cells, and enhancing autophagy in epithelial cells. Deregulation of complement system, degradation of antibacterial peptides, and destruction of phagocyte functions facilitate the evasion of P. gingivalis. Porphyromonas gingivalis can also suppress adaptive immunity, which allows P. gingivalis to exist in the host tissues and cause the inflammatory response persistently. Here, we review studies devoted to understanding the strategies utilized by P. gingivalis to escape host immunity. Methods for impairing P. gingivalis immune evasion are also mentioned.
Topics: Base Composition; Humans; Immune Evasion; Phylogeny; Porphyromonas gingivalis; Quality of Life; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 34254681
DOI: 10.1111/jre.12915 -
Molecular Oral Microbiology Aug 2021RagA and RagB proteins are major components of the outer membrane of the oral pathogen Porphyromonas gingivalis and, while recently suggested to represent a novel... (Review)
Review
RagA and RagB proteins are major components of the outer membrane of the oral pathogen Porphyromonas gingivalis and, while recently suggested to represent a novel peptide uptake system, their full function is still under investigation. Herein, we (a) discuss the evidence that the rag locus contributes to P. gingivalis virulence; (b) provide insight to Rag protein potential biological function in macromolecular transport and other aspects of bacterial physiology; (c) address the host response to Rag proteins which are immunodominant and immunomodulatory; and (d) review the potential of Rag-focused therapeutic strategies for the control of periodontal diseases.
Topics: Bacterial Proteins; Humans; Periodontal Diseases; Porphyromonas gingivalis; Virulence
PubMed: 34032024
DOI: 10.1111/omi.12345 -
Journal of Leukocyte Biology Oct 2020Discussion on the identification of an osteoclast precursor population, which emerges in the bone marrow after systemic infection with a periodontal pathogen.
Discussion on the identification of an osteoclast precursor population, which emerges in the bone marrow after systemic infection with a periodontal pathogen.
Topics: Osteoclasts; Porphyromonas gingivalis
PubMed: 33405332
DOI: 10.1002/JLB.3CE0720-364R -
Frontiers in Immunology 2023Atherosclerosis (AS) is a chronic inflammatory disease, involving a pathological process of endothelial dysfunction, lipid deposition, plaque rupture, and arterial... (Review)
Review
Atherosclerosis (AS) is a chronic inflammatory disease, involving a pathological process of endothelial dysfunction, lipid deposition, plaque rupture, and arterial occlusion, and is one of the leading causes of death in the world population. The progression of AS is closely associated with several inflammatory diseases, among which periodontitis has been shown to increase the risk of AS. (), presenting in large numbers in subgingival plaque biofilms, is the "dominant flora" in periodontitis, and its multiple virulence factors are important in stimulating host immunity. Therefore, it is significant to elucidate the potential mechanism and association between and AS to prevent and treat AS. By summarizing the existing studies, we found that promotes the progression of AS through multiple immune pathways. can escape host immune clearance and, in various forms, circulate with blood and lymph and colonize arterial vessel walls, directly inducing local inflammation in blood vessels. It also induces the production of systemic inflammatory mediators and autoimmune antibodies, disrupts the serum lipid profile, and thus promotes the progression of AS. In this paper, we summarize the recent evidence (including clinical studies and animal studies) on the correlation between and AS, and describe the specific immune mechanisms by which promotes AS progression from three aspects (immune escape, blood circulation, and lymphatic circulation), providing new insights into the prevention and treatment of AS by suppressing periodontal pathogenic bacteria.
Topics: Animals; Porphyromonas gingivalis; Periodontitis; Inflammation; Atherosclerosis; Lipids
PubMed: 36999040
DOI: 10.3389/fimmu.2023.1103592 -
Applied Biochemistry and Biotechnology Jan 2023Periodontitis, being a multifactorial disorder is found to be the most common oral disease denoted by the inflammation of gingiva and resorption of tooth supporting... (Review)
Review
Periodontitis, being a multifactorial disorder is found to be the most common oral disease denoted by the inflammation of gingiva and resorption of tooth supporting alveolar bone. The disease being closely linked with fast life style and determined by unhygienic behavioural factors, the internal milieu of oral cavity and formation of plaque biofilm on the dental and gingival surfaces. Porphyromonas gingivalis, being the major keystone pathogen of the periodontal biofilm evokes host immune responses that causes damage of gingival tissues and resorption of bones. The biofilm associated microbial community progressively aggravates the condition resulting in chronic inflammation and finally tooth loss. The disease often maintains bidirectional relationship with different systemic, genetic, autoimmune, immunodeficiency diseases and even psychological disorders. The disease can be diagnosed and predicted by various genetic, radiographic and computer-aided design (CAD) & computer-aided engineering (CAE) and artificial neural network (ANN). The elucidation of genetic background explains the inheritance of the disease. The therapeutic approaches commonly followed include mechanical removal of dental plaque with the use of systemic antibiotics. Awareness generation amongst local people, adoption of good practice of timely tooth brushing preferably with fluoride paste or with nanoconjugate pastes will reduce the chance of periodontal plaque formation. Modern tissue engineering technology like 3D bioprinting of periodontal tissue may help in patient specific flawless regeneration of tooth structures and associated bones.
Topics: Humans; Periodontitis; Inflammation; Gingiva; Porphyromonas gingivalis; Anti-Bacterial Agents
PubMed: 36098930
DOI: 10.1007/s12010-022-04127-9 -
Journal of Bacteriology Nov 2022Oral commensal streptococci are primary colonizers of the oral cavity. These streptococci produce many adhesins, metabolites, and antimicrobials that modulate microbial... (Review)
Review
Oral commensal streptococci are primary colonizers of the oral cavity. These streptococci produce many adhesins, metabolites, and antimicrobials that modulate microbial succession and diversity within the oral cavity. Often, oral commensal streptococci antagonize cariogenic and periodontal pathogens such as Streptococcus mutans and Porphyromonas gingivalis, respectively. Mechanisms of antagonism are varied and range from the generation of hydrogen peroxide, competitive metabolite scavenging, the generation of reactive nitrogen intermediates, and bacteriocin production. Furthermore, several oral commensal streptococci have been shown to alter the host immune response at steady state and in response to oral pathogens. Collectively, these features highlight the remarkable ability of oral commensal streptococci to regulate the structure and function of the oral microbiome. In this review, we discuss mechanisms used by oral commensal streptococci to interact with diverse oral pathogens, both physically and through the production of antimicrobials. Finally, we conclude by exploring the critical roles of oral commensal streptococci in modulating the host immune response and maintaining health and homeostasis.
Topics: Streptococcus; Streptococcus mutans; Mouth; Symbiosis; Porphyromonas gingivalis; Biofilms
PubMed: 36286512
DOI: 10.1128/jb.00257-22 -
Anaerobe Jun 2023With the buildup of new research data, newer associations between anaerobic bacteria and diseases/conditions were evaluated. The aim of the mini-review was to draw... (Review)
Review
With the buildup of new research data, newer associations between anaerobic bacteria and diseases/conditions were evaluated. The aim of the mini-review was to draw attention and to encourage further multidisciplinary studies of the associations. We considered microbiome-disease correlations such as a decrease of fecal Faecalibacterium prausnitzii abundance in inflammatory bowel disease (IBD) and IBD recurrence, suggesting that F. prausnitzii could be a good biomarker for IBD. A link of subgingival Porphyromonas gingivalis with cardiovascular diseases was reported. Decreased Roseburia abundance was observed in the gut of Alzheimer's and Parkinson's disease patients. Akkermansia muciniphila was found to improve adipose/glucose metabolism, however, its intestinal abundance was observed in neurodegenerative diseases as well. Severe Clostridioides difficile infections have been reported in neonates and young children. Carcinogenic potential of anaerobes has been suggested. Fusobacterium nucleatum was implicated in the development of oral and colorectal cancer, Porphyromonas gingivalis and Tannerella forsythia were linked to esophageal cancer and Cutibacterium acnes subsp. defendens was associated with prostate cancer. However, there are some controversies about the results. In a Swedish longitudinal study, neither P. gingivalis nor T. forsythia exhibited oncogenic potential. The present data can enrich knowledge of anaerobic bacteria and their multifaceted significance for health and disease and can draw future research directions. However, more studies on large numbers of patients over prolonged periods are needed, taking into account the possible changes in the microbiota over time.
Topics: Male; Child; Infant, Newborn; Humans; Child, Preschool; Bacteria, Anaerobic; Longitudinal Studies; Noncommunicable Diseases; Inflammatory Bowel Diseases; Microbiota; Porphyromonas gingivalis
PubMed: 37349047
DOI: 10.1016/j.anaerobe.2023.102714