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Archives of Oral Biology Apr 2024Periodontal bacteria can infiltrate the epithelium, activate signaling pathways, induce inflammation, and block natural killer and cytotoxic cells, all of which... (Review)
Review
INTRODUCTION
Periodontal bacteria can infiltrate the epithelium, activate signaling pathways, induce inflammation, and block natural killer and cytotoxic cells, all of which contribute to the vicious circle of carcinogenesis. It is unknown whether oral dysbiosis has an impact on the etiology or prognosis of OPMD.
AIMS
Within this paradigm, this work systemically investigated and reported on the composition of oral microbiota in patients with oral potentially malignant disorders (OPMD) versus healthy controls.
METHODS
Observational studies that reported next generation sequencing analysis of oral tissue or salivary samples and found at least three bacterial species were included. Identification, screening, citation analysis, and graphical synthesis were carried out.
RESULTS
For oral lichen planus (OLP), the bacteria with the highest abundance were Fusobacterium, Capnocytophaga, Gemella, Granulicatella, Porphyromonas, and Rothia; for oral leukoplakia (OLK), Prevotella. Streptococci levels in OLK and OLP were lower. The usage of alcohol or smoke had no effect on the outcomes.
CONCLUSIONS
An increase in periodontal pathogenic bacteria could promote the development and exacerbation of lichen. Effective bacteriome-based biomarkers are worthy of further investigation and application, as are bacteriome-based treatments.
Topics: Humans; Mouth Mucosa; Precancerous Conditions; Leukoplakia, Oral; Lichen Planus, Oral; Bacteria; Observational Studies as Topic
PubMed: 38295615
DOI: 10.1016/j.archoralbio.2024.105891 -
Frontiers in Cardiovascular Medicine 2023Periodontitis (PD) and cardiovascular diseases (CVD) rank among the most prevalent pathologies worldwide, and their correlation has been a subject of prolonged...
BACKGROUND
Periodontitis (PD) and cardiovascular diseases (CVD) rank among the most prevalent pathologies worldwide, and their correlation has been a subject of prolonged investigation. Numerous studies suggest shared etiological factors; however, a definitive causal connection remains unestablished. The objective of this study was to employ bibliometric and visual analyses in order to comprehensively examine the overarching characteristics, focal areas of research, and prospective trends pertaining to the PD-CVD relationship.
METHODS
We sourced articles, reviews, and online publications on PD- and CVD- research from the Web of Science Core Collection (WoSCC) spanning from January 1, 1993, to May 15, 2023. A triad of analytical tools (R-Bibliometrix, VOSviewer 1.6.19, and CiteSpace 6.2.R3) were utilized to facilitate collaboration network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection.
RESULTS
Out of the 1,116 publications that fulfilled the eligibility criteria in the WoSCC database, the comprehensive characteristics analysis divulged a sustained growth trend in publication frequency. In the cluster analysis of reference co-citation and keyword co-occurrence, prominent themes such as "periodontitis", "cardiovascular diseases", "inflammation", "", and "atherosclerosis" consistently emerged. Contemporary topics such as "peri-implantitis," "COVID-19", "cardiovascular risk factors," and "endocarditis" were pinpointed as burgeoning research hotspots.
CONCLUSION
Based on this bibliometric study, in the field of association studies between PD and CVD, the etiologic mechanisms of both diseases have been intensively studied in the last three decades. Periodontal pathogens might serve as potential initiating factors linking PD and CVD. Inflammation may constitute a significant etiological factor shared by both diseases. Several emerging topics, such as COVID-19 and peri-implantitis, exhibit promising potential. This exhaustive overview casts light on pivotal research arenas, augmenting the field's understanding and stimulating further scholarly investigations.
PubMed: 37745126
DOI: 10.3389/fcvm.2023.1255722 -
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 -
Activation of receptor-interacting protein 3-mediated necroptosis accelerates periodontitis in mice.Oral Diseases May 2024To investigate the involvement and role of receptor-interacting protein 3 (RIP3)-mediated necroptosis in periodontitis.
OBJECTIVE
To investigate the involvement and role of receptor-interacting protein 3 (RIP3)-mediated necroptosis in periodontitis.
METHODS
A periodontitis murine model was established by oral infection with Porphyromonas gingivalis, and activation of necroptosis pathway was identified by immunohistochemistry. Adeno-associated virus was used to knock down Rip3 and the effect of Rip3 knockdown on periodontal inflammation was examined by Micro-CT, qRT-PCR and histological staining. In vitro, P. gingivalis-LPS was used to infect fibroblast cell line L929 and siRNA was used to knock down Rip3. Necroptosis pathway signalling and inflammation in cells were detected by cell viability and death assay, Western Blot, qRT-PCR and immunofluorescence analysis.
RESULTS
Phosphorylation of RIP3 and mixed lineage kinase domain-like protein (MLKL) was increased in the periodontal ligament of mice infected with P. gingivalis. RIP3 knockdown reduced osteoclastogenesis and inflammatory cytokines in the periodontal area, and alleviated alveolar bone loss in vivo. In vitro, P. gingivalis-LPS-induced RIP3-mediated necroptosis in L929 cells, and knockdown of RIP3 by siRNA decreased the expression of inflammatory cytokines.
CONCLUSION
RIP3-mediated necroptosis is activated in periodontitis and blocking necroptosis alleviates disease progression, indicating that RIP3 may be a potential target for periodontitis treatment.
Topics: Animals; Necroptosis; Receptor-Interacting Protein Serine-Threonine Kinases; Mice; Periodontitis; Porphyromonas gingivalis; Disease Models, Animal; Cell Line; Mice, Inbred C57BL; Male; Bacteroidaceae Infections; Protein Kinases; Gene Knockdown Techniques; Periodontal Ligament; Phosphorylation; Cytokines; Alveolar Bone Loss
PubMed: 37518945
DOI: 10.1111/odi.14693 -
MSystems Aug 2023Periodontal disease is a chronic inflammatory disease in which the oral pathogen plays an important role. expresses virulence determinants in response to higher hemin...
Periodontal disease is a chronic inflammatory disease in which the oral pathogen plays an important role. expresses virulence determinants in response to higher hemin concentrations, but the underlying regulatory processes remain unclear. Bacterial DNA methylation has the potential to fulfil this mechanistic role. We characterized the methylome of , and compared its variation to transcriptome changes in response to hemin availability. W50 was grown in chemostat continuous culture with excess or limited hemin, prior to whole-methylome and transcriptome profiling using Nanopore and Illumina RNA-Seq. DNA methylation was quantified for Dam/Dcm motifs and all-context N6-methyladenine (6mA) and 5-methylcytosine (5mC). Of all 1,992 genes analyzed, 161 and 268 were respectively over- and under-expressed with excess hemin. Notably, we detected differential DNA methylation signatures for the Dam "GATC" motif and both all-context 6mA and 5mC in response to hemin availability. Joint analyses identified a subset of coordinated changes in gene expression, 6mA, and 5mC methylation that target genes involved in lactate utilization and ABC transporters. The results identify altered methylation and expression responses to hemin availability in , with insights into mechanisms regulating its virulence in periodontal disease. IMPORTANCE DNA methylation has important roles in bacteria, including in the regulation of transcription. , an oral pathogen in periodontitis, exhibits well-established gene expression changes in response to hemin availability. However, the regulatory processes underlying these effects remain unknown. We profiled the novel epigenome, and assessed epigenetic and transcriptome variation under limited and excess hemin conditions. As expected, multiple gene expression changes were detected in response to limited and excess hemin that reflect health and disease, respectively. Notably, we also detected differential DNA methylation signatures for the Dam "GATC" motif and both all-context 6mA and 5mC in response to hemin. Joint analyses identified coordinated changes in gene expression, 6mA, and 5mC methylation that target genes involved in lactate utilization and ABC transporters. The results identify novel regulatory processes underlying the mechanism of hemin regulated gene expression in with phenotypic impacts on its virulence in periodontal disease.
Topics: Humans; Hemin; Porphyromonas gingivalis; DNA Methylation; Periodontal Diseases; ATP-Binding Cassette Transporters; Gene Expression
PubMed: 37436062
DOI: 10.1128/msystems.01193-22 -
Clinical Oral Investigations Feb 2024Recent research has demonstrated that platelet-rich fibrin (PRF) is an appropriate carrier for ampicillin/sulbactam. The aim of the study was to investigate whether PRF...
OBJECTIVES
Recent research has demonstrated that platelet-rich fibrin (PRF) is an appropriate carrier for ampicillin/sulbactam. The aim of the study was to investigate whether PRF is also a suitable bio-carrier for clindamycin (CLI).
METHODS
PRF membranes were produced from 36 patients receiving intravenous therapy with CLI (e.g. due to the diagnosis of an osteonecrosis of the jaw or infections). Concentrations of CLI in PRF membranes were measured with liquid chromatography-tandem mass spectrometry, and the antimicrobial effects were investigated in vitro in agar diffusion tests with fresh PRF and PRF stored for 24 h. Storage was performed in an incubator at 36 °C to simulate the in-vivo situation.
RESULTS
The mean concentration of CLI in plasma was 1.0 ± 0.3 μg/100 mg plasma; in resulting PRF membranes 0.7 ± 0.4 μg/100 mg PRF. Agar diffusion tests were performed with Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus mitis, Porphyromonas gingivalis, and Fusobacterium nucleatum. Mean inhibition zones, in mm, for fresh PRF were 17.3, 12.2, 18.8, 17.1, 25.8 and 18.1, 12.7, 19.2, 17.3, and 26.3 for stored PRF, respectively.
CONCLUSION
The results demonstrate that PRF is a suitable bio-carrier for CLI when administered systemically to patients. The concentration in PRF generated from patients after infusion of 600 mg CLI dose suffices to target clinically relevant bacteria.
CLINICAL RELEVANCE
Using PRF as a carrier for local antibiotic application can prevent infections in oral and maxillofacial surgery. Within the study limitations, the findings could expand the scope of PRF application by adding CLI as a new antibiotic to the spectrum of PRF therapy.
Topics: Humans; Platelet-Rich Fibrin; Clindamycin; Agar; Anti-Bacterial Agents; Staphylococcus aureus
PubMed: 38351376
DOI: 10.1007/s00784-024-05532-6 -
Journal of Cellular Physiology Nov 2023Periodontitis is proposed as a risk factor for preterm delivery, fetal growth restriction, and preeclampsia with severe consequences for maternal and neonatal health,...
Periodontitis is proposed as a risk factor for preterm delivery, fetal growth restriction, and preeclampsia with severe consequences for maternal and neonatal health, but the biological mechanisms involved are elusive. Porphyromonas gingivalis gain access to the placental bed and impair trophoblast cell function, as assessed in murine and human pregnancy, suggesting a pathogenic role in adverse pregnancy and neonatal outcomes. P. gingivalis releases outer membrane vesicles (P. gingivalis OMV) during growth that spread to distant tissues and are internalized in host cells as described in metabolic, neurological, and vascular systemic diseases. Here we tested the hypothesis that P. gingivalis OMV internalized in trophoblast cells disrupt their metabolism leading to trophoblast and placenta dysfunction and adverse pregnancy outcomes. An in vitro design with human trophoblast cells incubated with P. gingivalis OMV was used together with ex vivo and in vivo approaches in pregnant mice treated with P. gingivalis OMV. P. gingivalis OMV modulated human trophoblast cell metabolism by reducing glycolytic pathways and decreasing total reactive oxygen species with sustained mitochondrial activity. Metabolic changes induced by P. gingivalis OMV did not compromise cell viability; instead, it turned trophoblast cells into a metabolic resting state where central functions such as migration and invasion were reduced. The effects of P. gingivalis OMV on human trophoblast cells were corroborated ex vivo in mouse whole placenta and in vivo in pregnant mice: P. gingivalis OMV reduced glycolytic pathways in the placenta and led to lower placental and fetal weight gain in vivo with reduced placental expression of the glucose transporter GLUT1. The present results point to OMV as a key component of P. gingivalis involved in adverse pregnancy outcomes, and even more, unveil a metabolic cue in the deleterious effect of P. gingivalis OMV on trophoblast cells and mouse pregnancy, providing new clues to understand pathogenic mechanisms in pregnancy complications and other systemic diseases.
Topics: Pregnancy; Female; Mice; Animals; Humans; Porphyromonas gingivalis; Trophoblasts; Pregnancy Outcome; Placenta; Periodontitis
PubMed: 37842869
DOI: 10.1002/jcp.31138 -
Frontiers in Oncology 2024Oral Squamous Cell Carcinoma (OSCC) is the most common type of head and neck cancer worldwide. Emerging research suggests a strong association between OSCC and the oral... (Review)
Review
Oral Squamous Cell Carcinoma (OSCC) is the most common type of head and neck cancer worldwide. Emerging research suggests a strong association between OSCC and the oral microbiota, a diverse community of bacteria, fungi, viruses, and archaea. Pathogenic bacteria, in particular and , have been closely linked to OSCC. Moreover, certain oral fungi, such as , and viruses, like the human papillomavirus, have also been implicated in OSCC. Despite these findings, the precise mechanisms through which the oral microbiota influences OSCC development remain unclear and necessitate further research. This paper provides a comprehensive overview of the oral microbiota and its relationship with OSCC and discusses potential carcinogenic pathways that the oral microbiota may activate or modulate are also discussed.
PubMed: 38375155
DOI: 10.3389/fonc.2024.1319777 -
Inflammation Oct 2023Periodontitis is a chronic inflammatory disease characterized by the destruction of tooth-supporting tissues. The gingival epithelium is the first barrier of periodontal...
Periodontitis is a chronic inflammatory disease characterized by the destruction of tooth-supporting tissues. The gingival epithelium is the first barrier of periodontal tissue against oral pathogens and harmful substances. The structure and function of epithelial lining are essential for maintaining the integrity of the epithelial barrier. Abnormal apoptosis can lead to the decrease of functional keratinocytes and break homeostasis in gingival epithelium. Interleukin-22 is a cytokine that plays an important role in epithelial homeostasis in intestinal epithelium, inducing proliferation and inhibiting apoptosis, but its role in gingival epithelium is poorly understood. In this study, we investigated the effect of interleukin-22 on apoptosis of gingival epithelial cells during periodontitis. Interleukin-22 topical injection and Il22 gene knockout were performed in experimental periodontitis mice. Human gingival epithelial cells were co-cultured with Porphyromonas gingivalis with interleukin-22 treatment. We found that interleukin-22 inhibited apoptosis of gingival epithelial cells during periodontitis in vivo and in vitro, decreasing Bax expression and increasing Bcl-xL expression. As for the underlying mechanisms, we found that interleukin-22 reduced the expression of TGF-β receptor type II and inhibited the phosphorylation of Smad2 in gingival epithelial cells during periodontitis. Blockage of TGF-β receptors attenuated apoptosis induced by Porphyromonas gingivalis and increased Bcl-xL expression stimulated by interleukin-22. These results confirmed the inhibitory effect of interleukin-22 on apoptosis of gingival epithelial cells and revealed the involvement of TGF-β signaling pathway in gingival epithelial cell apoptosis during periodontitis.
Topics: Humans; Mice; Animals; Epithelial Cells; Periodontitis; Apoptosis; Signal Transduction; Transforming Growth Factor beta; Gingiva; Porphyromonas gingivalis; Interleukin-22
PubMed: 37310646
DOI: 10.1007/s10753-023-01847-w -
The Journal of Allergy and Clinical... Feb 2024Airway microbiota in asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) remains unknown.
BACKGROUND
Airway microbiota in asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) remains unknown.
OBJECTIVE
This study with ACO-enriched population aimed to clarify airway microbiota in ACO and in mixed granulocytic inflammation, often detected in ACO and chronic airway diseases.
METHODS
This is an observational cross-sectional study. Patients with asthma with airflow limitation, ACO, and COPD were enrolled. Blood tests, pulmonary function, exhaled nitric oxide, and sputum tests were conducted. Sputum microbiota was evaluated using the 16S rRNA gene sequencing technique.
RESULTS
A total of 112 patients (13 asthma, 67 ACO, and 32 COPD) were examined. There were no significant differences in α-diversity among the 3 diseases. The relative abundances of phylum Bacteroidetes, class Bacteroidia, and genus were associated with decreased eosinophilic inflammation, and were significantly lower in ACO than in COPD. In a comparison of sputum inflammatory subtypes, the proportion of was numerically highest in the mixed granulocytic subtype, followed by the neutrophilic subtype. Likewise, the proportion of was the highest in the intermediate-high (2%-8%) sputum eosinophil group and lowest in the severe (≥8%) eosinophil group. Clinically, proportion was associated with sputum symptoms. Finally, the proportion of was associated with higher blood eosinophil counts and most severe airflow limitation.
CONCLUSIONS
Bacteroidia and abundances in sputum are associated with the eosinophil-low phenotype, and ACO may be characterized by a decrease in these taxa. A mild elevation in sputum eosinophil does not preclude the presence of , which should be noted in the management of obstructive airway diseases.
PubMed: 38155860
DOI: 10.1016/j.jacig.2023.100194