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Scientific Reports Aug 2022Dysbiosis of the oral microbiota plays an important role in the progression of periodontitis, which is characterized by chronic inflammation and alveolar bone loss, and...
Dysbiosis of the oral microbiota plays an important role in the progression of periodontitis, which is characterized by chronic inflammation and alveolar bone loss, and associated with systemic diseases. Bacterial extracellular vesicles (EVs) contain various bioactive molecules and show diverse effects on host environments depending on the bacterial species. Recently, we reported that EVs derived from Filifactor alocis, a Gram-positive periodontal pathogen, had osteoclastogenic activity. In the present study, we analysed the osteoclastogenic potency and immunostimulatory activity of EVs derived from the Gram-negative periodontal pathogens Porphyromonas gingivalis and Tannerella forsythia, the oral commensal bacterium Streptococcus oralis, and the gut probiotic strain Lactobacillus reuteri. Bacterial EVs were purified by density gradient ultracentrifugation using OptiPrep (iodixanol) reagent. EVs from P. gingivalis, T. forsythia, and S. oralis increased osteoclast differentiation and osteoclstogenic cytokine expression in osteoclast precursors, whereas EVs from L. reuteri did not. EVs from P. gingivalis, T. forsythia, and S. oralis preferentially activated Toll-like receptor 2 (TLR2) rather than TLR4 or TLR9, and induced osteoclastogenesis mainly through TLR2. The osteoclastogenic effects of EVs from P. gingivalis and T. forsythia were reduced by both lipoprotein lipase and polymyxin B, an inhibitor of lipopolysaccharide (LPS), while the osteoclastogenic effects of EVs from S. oralis were reduced by lipoprotein lipase alone. These results demonstrate that EVs from periodontal pathogens and oral commensal have osteoclastogenic activity through TLR2 activation by lipoproteins and/or LPS.
Topics: Cell Differentiation; Extracellular Vesicles; Lipopolysaccharides; Lipoprotein Lipase; Microbiota; Mouth; Osteoclasts; Porphyromonas gingivalis; Toll-Like Receptor 2; Toll-Like Receptor 4
PubMed: 35987920
DOI: 10.1038/s41598-022-18412-4 -
Scientific Reports Jul 2023The Arg-specific gingipains of Porphyromonas gingivalis RgpA and RgpB have 97% identical sequences in their catalytic domains yet their propeptides are only 76%...
The Arg-specific gingipains of Porphyromonas gingivalis RgpA and RgpB have 97% identical sequences in their catalytic domains yet their propeptides are only 76% identical. RgpA isolates as a proteinase-adhesin complex (HRgpA) which hinders direct kinetic comparison of RgpA as a monomer with monomeric RgpB. We tested modifications of rgpA identifying a variant that enabled us to isolate histidine-tagged monomeric RgpA (rRgpAH). Kinetic comparisons between rRgpAH and RgpB used benzoyl-L-Arg-4-nitroanilide with and without cysteine and glycylglycine acceptor molecules. With no glycylglycine, values of K, V, k and k/K for each enzyme were similar, but with glycylglycine K decreased, V increased and k increased ~ twofold for RgpB but ~ sixfold for rRgpAH. The k/K for rRgpAH was unchanged whereas that of RgpB more than halved. Recombinant RgpA propeptide inhibited rRgpAH and RgpB with K 13 nM and 15 nM K respectively slightly more effectively than RgpB propeptide which inhibited rRgpAH and RgpB with K 22 nM and 29 nM respectively (p < 0.0001); a result that may be attributable to the divergent propeptide sequences. Overall, the data for rRgpAH reflected observations previously made by others using HRgpA, indicating rRgpAH fidelity and confirming the first production and isolation of functional affinity tagged RgpA.
Topics: Gingipain Cysteine Endopeptidases; Cysteine Endopeptidases; Peptide Hydrolases; Adhesins, Bacterial; Catalytic Domain; Porphyromonas gingivalis; Hemagglutinins
PubMed: 37402780
DOI: 10.1038/s41598-023-37534-x -
Microbes and Infection 2023Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that can eventually lead to liver cirrhosis and hepatocellular carcinoma. Porphyromonas gingivalis...
Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that can eventually lead to liver cirrhosis and hepatocellular carcinoma. Porphyromonas gingivalis (P.g) is the main pathogen that causes periodontal disease, which participates in the development of NAFLD. The purpose of our study was to further study the direct role of P.g in NAFLD and the underlying molecular mechanism. An animal model of oral P.g administration was established, and liver function and pathology in this model were evaluated. The gut microbiome and metabolic products were analysed. Furthermore, the Th17/Treg balance in the spleen and liver was assessed. In our study, NAFLD was observed in all the mice that were orally administered P.g. The gut microbiome and metabolic products were altered after oral P.g administration. P.g and ferroptosis were observed in the livers of the mice after oral P.g administration. Additionally, ferroptosis was observed in hepatocytes in vitro, but it was reversed by ferroptosis inhibitors. In addition, P.g triggered an imbalance in the Th17/Treg ratio in the liver and spleen in vivo. These findings suggest that oral P.g administration directly induced NAFLD in mice, which may be dependent on the ferroptosis of liver cells that occurs through the Th17/Treg imbalance induced by disordered microbial metabolism. Therefore, improving the periodontal environment is a novel treatment strategy for preventing NAFLD.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Porphyromonas gingivalis; Ferroptosis; Mice, Inbred C57BL; Risk Factors; Liver; Metabolic Diseases
PubMed: 35987459
DOI: 10.1016/j.micinf.2022.105040 -
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 -
Medicina Oral, Patologia Oral Y Cirugia... Jul 2021Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them. (Review)
Review
BACKGROUND
Periodontitis may be associated with the development of head and neck cancer (HNC). A literature review was conducted to understand the possible association between them.
MATERIAL AND METHODS
Articles published in the PubMed database from January 1999 and May 2020 were retrieved. Limitations of the studies and biological mechanisms were discussed.
RESULTS
A total of 4,232 articles were found. Of these, 13 were analyzed according to inclusion criteria. Most papers found some association between periodontitis and HNC, although differences in periodontal evaluation, sample size, study design and tumor sites were observed. Porphyromonas gingivalis appears to increase the chance of both diseases, and it may be one of their main potential risk factors. Genetic predisposition is increased by exposure to environmental factors which can directly induce epigenetic changes that contribute to these diseases.
CONCLUSIONS
Understanding the mechanisms related to periodontitis and HNC has increased, however, well-designed clinical studies are needed for better conclusions. Furthermore, the advent of multiple "omic" technologies will help comprehend their possible association.
Topics: Head and Neck Neoplasms; Humans; Periodontitis; Porphyromonas gingivalis; Risk Factors
PubMed: 33340075
DOI: 10.4317/medoral.24270 -
International Journal of Molecular... Feb 2024Periodontitis is an inflammatory condition affecting the supporting structures of the teeth. Periodontal conditions may increase the susceptibility of individuals to... (Review)
Review
Periodontitis is an inflammatory condition affecting the supporting structures of the teeth. Periodontal conditions may increase the susceptibility of individuals to various systemic illnesses, including Alzheimer's disease. Alzheimer's disease is a neurodegenerative condition characterized by a gradual onset and progressive deterioration, making it the primary cause of dementia, although the exact cause of the disease remains elusive. Both Alzheimer's disease and periodontitis share risk factors and clinical studies comparing the associations and occurrence of periodontitis among individuals with Alzheimer's disease have suggested a potential correlation between these conditions. Brains of individuals with Alzheimer's disease have substantiated the existence of microorganisms related to periodontitis, especially , which produces neurotoxic gingipains and may present the capability to breach the blood-brain barrier. may induce tau hyperphosphorylation and lead to neuronal apoptosis. Lipopolysaccharides-components of bacterial cell membranes and mediators of inflammation-also have an impact on brain function. Further research could unveil therapeutic approaches targeting periodontal pathogens to potentially alleviate AD progression.
Topics: Humans; Alzheimer Disease; Periodontitis; Inflammation; Porphyromonas gingivalis; Risk Factors
PubMed: 38473858
DOI: 10.3390/ijms25052612 -
Italian Journal of Pediatrics Oct 2023Periodontal disease and its bacteria can be responsible for pregnancy complications and transmission of periodontal bacteria from mother to newborn.
BACKGROUND
Periodontal disease and its bacteria can be responsible for pregnancy complications and transmission of periodontal bacteria from mother to newborn.
METHODS
A salivary swab to 60 healthy, full-term newborns and their mothers was taken immediately after birth. The test was performed with Real Time PCR method to evaluate the expression of the gene through DNA amplification. The species considered were: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum ssp.
RESULTS
The newborn oral microbiome was composed primarily by saprophytes (98.38 + 4.88%), just like the mothers (98.8 + 3.69%). There was a statistically significant difference of the total microbiological density in newborns and mothers (p = 0.0001). Maternal and neonatal oral microbiome had a correlated total microbiological density only in 33.3% (N = 20/60) of cases. The analysis of the oral microbiome showed a pathological composition only in 12/60 babies (20%). The most frequent detected specie in newborns was Fusobacterium nucleatum (9/12 babies, 75%), as well as for the mothers (53.3%). However, the pathogen was present both in baby and his mother only in 3 dyads. Porphyromonas gingivalis showed the highest association mother-baby (4/12 dyads, 33%). Porphyromonas gingivalis was the pathogen with the highest bacterial load in the 12 mothers. We found a statistically significant difference in the total load of Porphyromonas gingivalis in mothers and babies (p = 0.02).
CONCLUSIONS
There was a statistically significant difference in the richness of the microbiome from newborns and mothers. Even comparing the microbiological density in the oral cavity of the individual mother-child pairs, we did not find a significant concordance. These results seem to suggest a low influence of maternal oral microbiome on the richness of the oral neonatal one. We didn't find mother-child concordance (p = 0.0001) in the presence of pathogenic periodontal micro-organisms. Fusobacterium nucleatum was the most frequent specie detected. Porphyromonas gingivalis instead was the bacteria with the higher possibility of transmission. In conclusion in our study maternal oral health doesn't affect healthy, full-term newborns' oral microbiome. Further studies are needed to understand the maternal influence on newborn's oral microbiome and its effects on babies long-term health.
Topics: Infant; Pregnancy; Female; Infant, Newborn; Humans; Porphyromonas gingivalis; Prevotella intermedia; Fusobacterium nucleatum; Mothers
PubMed: 37840153
DOI: 10.1186/s13052-023-01520-w -
A Boolean Network Approach to Study the Mechanism Associated with Inflammatory Response Induced by .Archives of Razi Institute Feb 2023Anaerobic is a rod-shaped bacterium and is a primary agent of periodontal inflammation and thus periodontitis. This bacterium disturbs the normal flora of the oral... (Review)
Review
Anaerobic is a rod-shaped bacterium and is a primary agent of periodontal inflammation and thus periodontitis. This bacterium disturbs the normal flora of the oral cavity and causes dysbiosis. Databases including Google Scholar Scopus and PubMed were employed to find the evidence by using keywords like ',' 'Boolean network,' 'inflammatory response and ,' 'inflammation and . Only articles that reviewed the role of in oral inflammation were selected. promotes and reorganizes host immune systems against normal host flora, which causes a dysbiotic state. A reorganized immune system induces dysbiosis and periodontitis. Specifically, the role of the C5a receptor in the complement system is vital in this mechanism. can change the metabolic pathways of phagocytic cells without impeding inflammation. Toll-like receptor and complement signaling are inverted by , which aids them in overcoming immunological responses. However, they sustain the inflammation process, which promotes dysbiosis. Instead of a subjective approach, a systems perspective is required to comprehend this intricate process. A Boolean network is a system approach that seems to be a better approach to understanding this complicated interaction process of with the immune system and inflammation. In short, attempts to understand the complex process using the Boolean network will ultimately help in the early detection of periodontitis, and immediate treatment can prevent soft tissue destruction and dentition loss.
Topics: Animals; Dysbiosis; Porphyromonas gingivalis; Inflammation; Hydrolases
PubMed: 37312726
DOI: 10.22092/ARI.2021.356604.1877