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Frontiers in Immunology 2024There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health.... (Review)
Review
There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health. Disruptions in the commensal flora can lead to oral diseases, while systemic illnesses can also impact the oral cavity, resulting in the development of oral diseases and disorders. and , known as pathogenic bacteria associated with periodontitis, play a crucial role in linking periodontitis to accompanying systemic diseases. In periodontal tissues, these bacteria, along with their virulence factors, can excessively activate the host immune system through local diffusion, lymphatic circulation, and blood transmission. This immune response disruption contributes to an imbalance in osteoimmune mechanisms, alveolar bone resorption, and potential systemic inflammation. To restore local homeostasis, a deeper understanding of microbiota-host interactions and the immune network phenotype in local tissues is imperative. Defining the immune network phenotype in periodontal tissues offers a promising avenue for investigating the complex characteristics of oral plaque biofilms and exploring the potential relationship between periodontitis and associated systemic diseases. This review aims to provide an overview of the mechanisms underlying - and -induced alveolar bone resorption, as well as the immunophenotypes observed in host periodontal tissues during pathological conditions.
Topics: Humans; Periodontitis; Alveolar Bone Loss; Porphyromonas gingivalis; Inflammation; Fusobacterium nucleatum
PubMed: 38455060
DOI: 10.3389/fimmu.2024.1254516 -
Journal of Histotechnology Sep 2023Diabetes and periodontitis are prevalent diseases that considerably impact global economy and diabetes is a major risk factor of periodontitis. Mitochondrial dynamic...
Diabetes and periodontitis are prevalent diseases that considerably impact global economy and diabetes is a major risk factor of periodontitis. Mitochondrial dynamic alterations are involved in many diseases including diabetes and this study aims to evaluate their relevance with diabetes aggravated periodontitis. Sixty mice are randomly divided into 4 groups: control, periodontitis, diabetes and diabetic periodontitis. Periodontitis severity is evaluated by alveolar bone loss, inflammation and oxidative stress status. Mitochondrial structural and functional defects are evaluated by the mitochondrial fission/fusion events, mitochondrial reactive oxygen species (ROS) accumulation, complex activities and adenosine triphosphate (ATP) production. Advanced glycation end product (AGE) and are closely related to periodontitis occurrence and development. Human gingival fibroblast cells (HGF-1) are used to investigate the AGE role and lipopolysaccharide (LPS) from (P-LPS) in aggravating diabetic periodontitis by mitochondrial dynamic and function alterations. In vivo, diabetic mice with periodontitis show severe bone loss, increased inflammation and oxidative stress accumulation. Among mice with periodontitis, diabetic mice show worse mitochondrial dynamic perturbations than lean mice, along with fusion protein levels inducing more mitochondrial fission in gingival tissue. In vitro, AGEs and P-LPS co-treatment causes severe.
Topics: Mice; Humans; Animals; Mitochondrial Dynamics; Diabetes Mellitus, Experimental; Lipopolysaccharides; Periodontitis; Inflammation; Porphyromonas gingivalis
PubMed: 37184352
DOI: 10.1080/01478885.2023.2188705 -
Critical Reviews in Microbiology Mar 2020(), a Gram-negative facultative anaerobe of the oral cavity, is associated with the onset of various adverse pregnancy outcomes. is linked with the development of... (Review)
Review
(), a Gram-negative facultative anaerobe of the oral cavity, is associated with the onset of various adverse pregnancy outcomes. is linked with the development of preeclampsia, preterm labour, spontaneous abortion, gestational diabetes, foetal growth restriction, and misconception. The unique virulence factors, surface adhesions, enzymes of can directly injure and alter the morphology, microbiome the foetal and maternal tissues. can even exaggerate the production of cytokines, free radicals and acute-phase proteins in the uterine compartment that increases the risk of myometrial contraction and onset of preterm labour. Although evidence confirms the presence of in the amniotic fluid and placenta of women with poor pregnancy outcomes, the intricate molecular mechanisms by which initiates various antenatal and postnatal maternal and foetal complications are not well explained in the literature. Therefore, the present review aims to comprehensively summarise and highlight the recent and unique molecular pathogenic mechanisms of associated with adverse pregnancy outcomes.
Topics: Animals; Bacteroidaceae Infections; Cytokines; Female; Humans; Mouth; Porphyromonas gingivalis; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 32267781
DOI: 10.1080/1040841X.2020.1747392 -
Journal of Dental Research Apr 2022, and species found in severe periodontitis use the Type IX Secretion System (T9SS) to load their outer membrane surface with an array of virulence factors. These... (Review)
Review
, and species found in severe periodontitis use the Type IX Secretion System (T9SS) to load their outer membrane surface with an array of virulence factors. These virulence factors are then released on outer membrane vesicles (OMVs), which penetrate the host to dysregulate the immune response to establish a positive feedback loop of chronic, inflammatory destruction of the tooth's supporting tissues. In this review, we present the latest information on the molecular architecture of the T9SS and provide mechanistic insight into its role in secretion and attachment of cargo proteins to produce a virulence coat on cells and OMVs. The recent molecular structures of the T9SS motor comprising PorL and PorM as well as the secretion pore Sov, together with advances in the overall interactome, have provided insight into the possible mechanisms of secretion. We propose the presence of PorL/M motors arranged in a circle at the inner membrane with bent periplasmic rotors interacting with the PorN protein. At the outer membrane, we envisage a slide carousel model where the PorN protein is driven around a circular track composed of PorK. Cargo proteins are transported by PorN to PorW and the Sov translocon just as slides are rotated to the projection window. Secreted proteins are proposed to then be shuttled along highways consisting of the PorV shuttle protein to an array of attachment complexes distributed around the cell. The cell surface attachment of cargo is a hallmark of the T9SS, and in and , this attachment is achieved via covalent bonding to a linking sugar synthesized by the Wbp/Vim pathway. The cell-surface attached cargo are enriched on OMVs, which are then released from the cell.
Topics: Bacterial Proteins; Bacterial Secretion Systems; Porphyromonas gingivalis; Tannerella forsythia; Virulence Factors
PubMed: 34889148
DOI: 10.1177/00220345211051599 -
Molecular Oral Microbiology Aug 2020Inflammasomes are multiprotein complexes that regulate immune processes in response to infections and tissue damage. They modulate Interleukin-1beta (IL-1β) expression,...
INTRODUCTION
Inflammasomes are multiprotein complexes that regulate immune processes in response to infections and tissue damage. They modulate Interleukin-1beta (IL-1β) expression, a major proinflammatory cytokine. The inflammasome/IL-1β pathway is involved in head and neck squamous cell carcinoma (HNSCC) progression and the periodontal pathogens Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) have been reported to cause chronic inflammation in HNSCC. The aim of this study was to characterise the role of these pathogens in regulating inflammasome activity and the IL-1β response in HNSCC in vitro.
METHODS
An HNSCC cell line (H400) was exposed to Fn and Pg individually or in combination for 24h, ± incubation for 30 min with 5 mM adenosine triphosphate (ATP). Transcript levels of inflammasomes, NLRP3 and AIM2; inflammasome-regulatory proteins, POP1, CARD16 and TRIM16; and inflammasome-component, ASC and caspase 1 and IL-1β, were assayed by RT-PCR. Expression of IL-1β was by immunocytochemistry and ELISA.
RESULTS
NLRP3 expression was significantly upregulated in response to Pg, Fn + Pg, Pg + ATP and Fn + Pg + ATP. AIM2 was significantly upregulated by Fn, Pg and Fn + Pg + ATP exposure. All conditions significantly upregulated IL-1β gene expression. POP1 expression was significantly downregulated by Pg or Fn exposure but not by Fn + Pg. Intracellular pro- and mature IL-1β were significantly higher following Fn and Pg + ATP exposure.
CONCLUSION
Pg alone increased IL-1β by upregulating AIM2, NLRP3 and downregulating POP1. Fn promoted IL-1β by increasing AIM2 and downregulating POP1. Pg + ATP with or without Fn upregulated NLRP3, IL-1β by downregulating POP1. Periodontal pathogens may contribute to HNSCC pathogenesis by increasing the IL-1β response due to inflammasome dysregulation.
Topics: Caspase 1; Fusobacterium nucleatum; Inflammasomes; Interleukin-1beta; NLR Family, Pyrin Domain-Containing 3 Protein; Porphyromonas gingivalis
PubMed: 32516848
DOI: 10.1111/omi.12302 -
The Journal of Infectious Diseases Jan 2024Periodontitis is an exemplar of dysbiosis associated with the coordinated action of multiple members within the microbial consortium. The polymicrobial synergy and...
Periodontitis is an exemplar of dysbiosis associated with the coordinated action of multiple members within the microbial consortium. The polymicrobial synergy and dysbiosis hypothesis proposes a dynamic host-microbiome balance, with certain modulators capable of disrupting eubiosis and driving shifts towards dysbiosis within the community. However, these factors remain to be explored. We established a Porphyromonas gingivalis- or Aggregatibacter actinomycetemcomitans-modified subgingival microbiome model and 16S rRNA sequencing revealed that P. gingivalis and A. actinomycetemcomitans altered the microbiome structure and composition indicated by α and β diversity metrics. P. gingivalis increased the subgingival dysbiosis index (SDI), while A. actinomycetemcomitans resulted in a lower SDI. Furthermore, P. gingivalis-stimulated microbiomes compromised epithelium function and reduced expression of tight junction proteins, whereas A. actinomycetemcomitans yielded mild effects. In conclusion, by inoculating P. gingivalis, we created dysbiotic microcosm biofilms in vitro resembling periodontitis-related subgingival microbiota, exhibiting enhanced dysbiosis and impaired epithelium integrity.
Topics: Humans; Porphyromonas gingivalis; Aggregatibacter actinomycetemcomitans; RNA, Ribosomal, 16S; Dysbiosis; Periodontitis; Microbiota
PubMed: 37855446
DOI: 10.1093/infdis/jiad461 -
Progress in Orthodontics Jun 2020Because changes in surface properties affect bacterial adhesion, orthodontic bonding procedures may significantly influence biofilm formation and composition around...
BACKGROUND
Because changes in surface properties affect bacterial adhesion, orthodontic bonding procedures may significantly influence biofilm formation and composition around orthodontic appliances. However, most studies used a mono-species biofilm model under static conditions, which does not simulate the intraoral environment and complex interactions of oral microflora because the oral cavity is a diverse and changeable environment. In this study, a multi-species biofilm model was used under dynamic culture conditions to assess the effects of the orthodontic bonding procedure on biofilm formation and compositional changes in two main oral pathogens, Streptococcus mutans and Porphyromonas gingivalis.
METHODS
Four specimens were prepared with bovine incisors and bonding adhesive: untreated enamel surface (BI), enamel surface etched with 37% phosphoric acid (ET), primed enamel surface after etching (PR), and adhesive surface (AD). Surface roughness (SR), surface wettability (SW), and surface texture were evaluated. A multi-species biofilm was developed on each surface and adhesion amounts of Streptococcus mutans, Porphyromonas gingivalis, and total bacteria were analyzed at day 1 and day 4 using real-time polymerase chain reaction. After determining the differences in biofilm formation, SR, and SW between the four surfaces, relationships between bacteria levels and surface properties were analyzed.
RESULTS
The order of SR was AD < PR < BI < ET, as BI and ET showed more irregular surface texture than PR and AD. For SW, ET had the greatest value followed by PR, BI, and AD. S. mutans and P. gingivalis showed greater adhesion to BI and ET with rougher and more wettable surfaces than to AD with smoother and less wettable surfaces. The adhesion of total bacteria and S. mutans significantly increased over time, but the amount of P. gingivalis decreased. The adhesion amounts of all bacteria were positively correlated with SR and SW, irrespective of incubation time.
CONCLUSIONS
Within the limitations of this study, changes in SR and SW associated with orthodontic bonding had significant effects on biofilm formation and composition of S. mutans and P. gingivalis.
Topics: Animals; Bacterial Adhesion; Biofilms; Cattle; Porphyromonas gingivalis; Streptococcus mutans; Surface Properties
PubMed: 32476070
DOI: 10.1186/s40510-020-00314-8 -
Clinical and Experimental Dental... Feb 2022The objective of this study was to introduce the evidence obtained through extensive research that periodontitis increases risk of many systemic diseases. (Review)
Review
OBJECTIVES
The objective of this study was to introduce the evidence obtained through extensive research that periodontitis increases risk of many systemic diseases.
METHOD
Analysis of some oral bacteria (P. gingivalis, T. denticola, T. forsythia, A. actinomycetemcomitans, and F. nucleatum) and its related treatments and mediators by the specific methods (western blot, ELISA, etc).
RESULTS
This article reviews in detail the evidence obtained through extensive research that periodontitis increases risk of many systemic diseases, including cardiovascular disease, rheumatoid arthritis, and Alzheimer's disease. These diseases are known to be associated with some certain specific gram-negative bacteria as periodontal pathogens, which induce inflammation and related diseases through TLR receptors, kinases, transcriptional factors and other cytokines. We also reviewed the latest research for inhibitors against inflammation and related diseases that have potential to be further applied clinically. In addition, based on a large amount of research evidence, we draw two tables about the mechanism of disease caused by periodontal bacteria, so that readers can easily search and analyze these research results.
DISCUSSION
This review details how the periodontal bacteria and their virulence factors can trigger host immune defense and induce many systemic diseases via inflammation and invasion. This Review also addressed the latest research around inhibitors against inflammation.
Topics: Aggregatibacter actinomycetemcomitans; Humans; Inflammation; Periodontitis; Porphyromonas gingivalis
PubMed: 34626163
DOI: 10.1002/cre2.499 -
Research in Microbiology 2022The phosphopantetheinyl transferases (PPTases) catalyze the post-translational modification of carrier proteins (CPs) from fatty acid synthases (FASs) in primary...
The phosphopantetheinyl transferases (PPTases) catalyze the post-translational modification of carrier proteins (CPs) from fatty acid synthases (FASs) in primary metabolism and from polyketide synthases (PKSs) and non-ribosomal polypeptide synthases (NRPSs) in secondary metabolism. Based on the conserved sequence motifs and substrate specificities, two types (AcpS-type and Sfp-type) of PPTases have been identified in prokaryotes. We present here that Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, harbors merely one PPTase, namely PptP. Complementation and gene deletion experiments clearly show that PptP can replace the function of Escherichia coli AcpS and is essential for the growth of P. gingivalis. Purified PptP transfers the 4-phosphopantetheine moiety of CoA to inactive apo-acyl carrier protein (ACP) to form holo-ACP, which functions as an active carrier of the acyl intermediates of fatty acid synthesis. Moreover, PptP exhibits broad substrate specificity, modifying all ACP substrates tested and catalyzing the transfer of coenzyme A (CoA) derivatives. The lack of sequence alignment with known PPTases together with phylogenetic analyses revealed PptP as a new class of PPTases. Identification of the new PPTase gene pptP exclusive in Porphyromonas species reveals a potential target for treating P. gingivalis infections.
Topics: Acyl Carrier Protein; Bacterial Proteins; Coenzyme A; Escherichia coli; Phylogeny; Porphyromonas; Transferases (Other Substituted Phosphate Groups)
PubMed: 35337986
DOI: 10.1016/j.resmic.2022.103940 -
Deciphering the toxicological role of Porphyromonas gingivalis derived endotoxins in liver diseases.Environmental Toxicology and... Nov 2021Periodontitis is a most prevalent and infectious multifactorial inflammatory disease and is characterized by the progressive destruction of the tooth-supporting tissues.... (Review)
Review
Periodontitis is a most prevalent and infectious multifactorial inflammatory disease and is characterized by the progressive destruction of the tooth-supporting tissues. Porphyromonas gingivalis, a Gram‑negative oral anaerobe, mainly causes periodontitis and it is one of the most important risk factors responsible for aggravation of existing systemic diseases. Several experimental and clinical studies have shown the positive association between periodontitis and different forms of liver disease. Periodontal diseases increase the prevalence of non-alcoholic fatty liver diseases and cirrhosis. Infected periodontium and pathogens in the periodontal microenvironments release pathogen-associated molecular patterns such as peptidoglycan, lipopolysaccharides, gingipain, fimbria, bacterial DNA, etc, and damage-associated molecular patterns such as interleukins-1α, β, - 8, and galectin-3, etc. These virulence factors and cytokines enter the bloodstream, disseminate into the whole body, and induce a variety of systemic pathological effects, including liver diseases (steatosis and fibrosis). Maintaining oral hygiene by scaling and root planning significantly improves liver damage in patients with periodontitis. Dentists and physicians should have more awareness in understanding the bidirectional nature of the relationship between oral and systemic diseases. Importantly, periodontitis condition aggravates simple fatty liver into fibrotic disease and therefore, the aim of this review is to understand the possible link between periodontitis and liver diseases.
Topics: Animals; Bacteroidaceae Infections; Endotoxins; Humans; Life Style; Liver Diseases; Oral Hygiene; Periodontitis; Porphyromonas gingivalis
PubMed: 34662732
DOI: 10.1016/j.etap.2021.103755