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1.
Int J Mol Sci ; 23(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36077282

RESUMO

Rheumatoid arthritis (RA) and periodontitis are suggested to be closely linked based on microbial dysbiosis, but limited subgingival bacteria have been proven in the pathogenesis of RA. We enrolled 30 RA patients and 25 controls and divided them into three groups with matched age, gender, and diabetes statuses: group AM (all of the matched participants), group PD (periodontally diseased), and group PH (periodontally healthy). Their subgingival microbial composition was determined by V3-V4 16S rRNA gene sequencing. Significant differences in subgingival microbial clustering between the RA patients and controls were observed in groups AM and PD. Among the taxa enriched in RA, Aminipila butyrica and Peptococcus simiae were the only two species displaying positive correlation to the level of anti-citrullinated protein antibodies (ACPAs) in both of the groups. Surprisingly, the median of relative abundances of A. butyrica and P. simiae were 0% in the controls of group PD. Furthermore, a gene encoding arginine deiminase with the capability to produce citrulline was addressed in the complete genome sequence of A. butyrica. This is the first study to elucidate the important roles of A. butyrica and P. simiae as periodontal bacteria leading to RA possibly through the induction of ACPA production.


Assuntos
Artrite Reumatoide , Microbiota , Periodontite , Anticorpos Anti-Proteína Citrulinada , Autoanticorpos , Bactérias/genética , Humanos , Microbiota/genética , Periodontite/microbiologia , RNA Ribossômico 16S/genética
2.
Sci Rep ; 12(1): 15895, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151274

RESUMO

The oral microbial profile in humans has evolved in response to lifestyle changes over the course of different eras. Here, we investigated tooth lesions and the microbial profile of periodontal bacteria (PB) in dental calculus of a Sardinian pre-industrial rural community. In total, 51 teeth belonging to 12 historical individuals buried in an ossuary in the early 1800s and 26 modern teeth extracted from 26 individuals from the same geographical area were compared to determine the oral health status, bacterial load and amount of most relevant PB. Total caries and bacterial genomes count appeared to be sex-related in historical samples. Historical females presented a higher incidence of caries, PB pathogens and a higher bacterial load than historical males. Furthermore, we compared the PB profile of the historical individuals with the modern ones, revealing a notable increase in modern individuals of PB belonging to "Red complex bacteria" often associated with periodontitis and other chronic diseases of modern life. Our findings could be explained through an analysis of environmental factors such as socioeconomic, hygienic and healthy conditions that can have a great impact on oral health and bacterial composition among individuals of the same and different eras.


Assuntos
Cárie Dentária , Doenças Periodontais , Periodontite , Dente , Bactérias/genética , Cárie Dentária/epidemiologia , Feminino , Humanos , Masculino , Saúde Bucal , Doenças Periodontais/epidemiologia , Periodontite/microbiologia , População Rural
3.
Front Immunol ; 13: 980805, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091038

RESUMO

Observations from numerous clinical, epidemiological and serological studies link periodontitis with severity and progression of rheumatoid arthritis. The strong association is observed despite totally different aetiology of these two diseases, periodontitis being driven by dysbiotic microbial flora on the tooth surface below the gum line, while rheumatoid arthritis being the autoimmune disease powered by anti-citrullinated protein antibodies (ACPAs). Here we discuss genetic and environmental risk factors underlying development of both diseases with special emphasis on bacteria implicated in pathogenicity of periodontitis. Individual periodontal pathogens and their virulence factors are argued as potentially contributing to putative causative link between periodontal infection and initiation of a chain of events leading to breakdown of immunotolerance and development of ACPAs. In this respect peptidylarginine deiminase, an enzyme unique among prokaryotes for Porphyromonas gingivalis, is elaborated as a potential mechanistic link between this major periodontal pathogen and initiation of rheumatoid arthritis development.


Assuntos
Anticorpos Anti-Proteína Citrulinada , Artrite Reumatoide , Periodontite , Desiminases de Arginina em Proteínas , Anticorpos Anti-Proteína Citrulinada/genética , Anticorpos Anti-Proteína Citrulinada/imunologia , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Autoanticorpos/genética , Autoanticorpos/imunologia , Humanos , Periodontite/complicações , Periodontite/genética , Periodontite/imunologia , Periodontite/microbiologia , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/genética , Desiminases de Arginina em Proteínas/genética , Desiminases de Arginina em Proteínas/imunologia
4.
Microb Pathog ; 171: 105724, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35988883

RESUMO

Oral microbes coexist with each other in a symbiotic relationship or as commensals in healthy body. Teeth and oral cavity harbor diverse community of fungi and bacteria. This study focused on bacterial and fungal component of gingiva, where the last occupy little attention. In addition to study the antimicrobial activity of toothpastes, mouth washes and natural oils against microorganisms. Sixty swabs from outer surfaces of gingiva in healthy persons, as well as patients complaining of gingivitis and periodontitis were collected for fungal and bacterial analyses. Sensitivity of the isolated microorganisms to some pharmaceutical preparations and natural oils was also performed. Ten fungal and 9 bacterial species were identified. There is a highly significant variation in the frequency of Klebsiella pneumonia among healthy, gingivitis and periodontitis. Also, Candida tropicalis and cocci bacteria showed significant diversity among the three tested groups. Among pharmaceutical preparations (toothpastes and mouth washes) and natural oils, Paradontax, Hexitol and clove oil showed the best antimicrobial activity against tested fungal and bacterial strains. Although, minimum inhibition concentrations (MICs) of clove oil were high compared to Paradontax and Hexitol, nevertheless, it is highly recommended as both antifungal and antibacterial agent against oral pathogenic microorganisms, because it is a natural compound and nearly devoid of side effects.


Assuntos
Gengivite , Microbiota , Periodontite , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias , Óleo de Cravo/farmacologia , Gengiva/microbiologia , Gengivite/microbiologia , Humanos , Periodontite/microbiologia , Preparações Farmacêuticas , Óleos Vegetais , Álcoois Açúcares , Cremes Dentais
5.
PLoS One ; 17(8): e0272148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35994451

RESUMO

This study explores the risk for cancer by level of antibodies to the anaerobe oral bacteria of periodontitis Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all three collectively termed the red complex, and the facultative anaerobe bacterium Aggregatibacter actinomycetemcomitans (AA). The prospective cohort, the Oslo II-study from 2000, the second screening of the Oslo study of 1972/73, has been followed for 17 ½ years with regard to cancer incidence and mortality. A random sample of 697 elderly men comprised the study cohort. The antibody results measured by enzyme linked immunosorbent assay (ELISA) were used in the Cox proportional hazards analyses, and quartile risk on cancer incidence in a 17 ½ years follow-up. Among the 621 participants with no prior cancer diagnoses, 221 men developed cancer. The incidence trend was inverse, and the results are shown as 1st quartile of highest value and 4th as lowest of antibody levels. The results of the Cox proportional regression analyses showed that TF inversely predicts bladder cancer (n = 22) by Hazard Ratio (HR) = 1.71 (95% CI: 1.12, 2.61). TD inversely predicts colon cancer (n = 26) by HR = 1.52 (95% CI: 1.06, 2.19) and bladder cancer (n = 22) by HR = 1.60 (95% CI: 1.05, 2.43). Antibodies to two oral bacteria, TF and TD, showed an inverse risk relationship with incidence of specific cancers: TF bladder cancer, TD bladder and colon cancer. Lowered immunological response to the oral infection, periodontitis, is shown to be a risk factor in terms of cancer aetiology.


Assuntos
Neoplasias do Colo , Periodontite , Neoplasias da Bexiga Urinária , Idoso , Aggregatibacter actinomycetemcomitans , Feminino , Humanos , Masculino , Periodontite/microbiologia , Porphyromonas gingivalis , Estudos Prospectivos , Tannerella forsythia , Treponema denticola
6.
Front Immunol ; 13: 952040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35967399

RESUMO

Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. P. gingivalis has recently been detected in rheumatoid arthritis (RA), cardiovascular disease, and tumors, as well as Alzheimer's disease (AD), and the presence of P. gingivalis in these diseases are correlated with poor prognosis. Macrophages are major innate immune cells which modulate immune responses against pathogens, however, multiple bacteria have evolved abilities to evade or even subvert the macrophages' immune response, in which subsequently promote the diseases' initiation and progression. P. gingivalis as a keystone pathogen of periodontitis has received increasing attention for the onset and development of systemic diseases. P. gingivalis induces macrophage polarization and inflammasome activation. It also causes immune response evasion which plays important roles in promoting inflammatory diseases, autoimmune diseases, and tumor development. In this review, we summarize recent discoveries on the interaction of P. gingivalis and macrophages in relevant disease development and progression, such as periodontitis, atherosclerosis, RA, AD, and cancers, aiming to provide an in-depth mechanistic understanding of this interaction and potential therapeutic strategies.


Assuntos
Artrite Reumatoide , Periodontite , Humanos , Inflamassomos , Ativação de Macrófagos , Macrófagos , Periodontite/microbiologia , Porphyromonas gingivalis
7.
PLoS One ; 17(8): e0273523, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35998186

RESUMO

No microbiological criteria were included in the 2018 EFP-AAP classification of periodontal diseases that could be used to differentiate between stages and grades. Furthermore, differences in the subgingival microbiome depending on stage and grade have not been established. Sixty subgingival biofilm samples were collected in Spain (n = 30) and Colombia (n = 30) from three distinct patient categories: those with periodontal health/gingivitis (n = 20), those with stage I-II periodontitis (n = 20), and those with stage III-IV periodontitis (n = 20). Patients were evaluated by 16S rRNA gene amplification sequencing. Amplicon sequence variants were used to assign taxonomic categories compared to the Human Oral Microbiome Database (threshold ≥97% identity). Alpha diversity was established by Shannon and Simpson indices, and principal coordinate analysis, ANOSIM, and PERMANOVA of the UNIFRAC distances were performed using QIIME2. Although differences in the alpha diversity were observed between samples according to country, Filifactor alocis, Peptostreptococcaceae [XI][G-4] bacterium HMT 369, Fretibacterium fastidiosum, Lachnospiraceae [G-8] bacterium HMT 500, Peptostreptococcaceae [XI][G-5] [Eubacterium] saphenum, Peptostreptococcus stomatis, and Tannerella forsythia were associated with periodontitis sites in all stages. However, only F. alocis, Peptostreptococcaceae [XI][G-4] bacterium HMT 369, Peptostreptococcaceae [XI][G-9] [Eubacterium] brachy, Peptostreptococcaceae [XI][G-5] [Eubacterium] saphenum, and Desulfobulbus sp. HMT 041 were consistent in stage III-IV periodontitis in both countries. Porphyromonas gingivalis and Tannerella forsythia were differentially expressed in severe lesions in the countries studied. Although some non-cultivable microorganisms showed differential patterns between the different stages of periodontitis, they were not the same in the two countries evaluated. Further studies using larger samples with advanced next-generation techniques for high-throughput sequencing of phyla and non-cultivable bacteria within the subgingival microbiome could provide more insight into the differences between stages of periodontitis.


Assuntos
Gengivite , Microbiota , Periodontite , Eubacterium , Humanos , Microbiota/genética , Periodontite/microbiologia , Porphyromonas gingivalis/genética , RNA Ribossômico 16S/genética
8.
Mol Oral Microbiol ; 37(5): 180-195, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35861180

RESUMO

Periodontitis is a chronic inflammatory disease associated with the presence of dysbiotic microbial communities. Several studies interrogating periodontitis pathogenesis have utilized the murine ligature-induced periodontitis (LIP) model and have further examined the ligature-associated microbiome relying on 16S rRNA-based sequencing techniques. However, it is often very challenging to compare microbial profiles across studies due to important differences in bioinformatic processing and databases used for taxonomic assignment. Thus, our study aim was to reanalyze microbiome sequencing datasets from studies utilizing the LIP model through a standardized bioinformatic analysis pipeline, generating a comprehensive overview of microbial dysbiosis during experimental periodontitis.We conducted a reanalysis of 16S rDNA gene sequencing datasets from nine published studies utilizing the LIP model. Reads were grouped according to the hypervariable region of the 16S rDNA gene amplified (V1-V3 and V4), preprocessed, binned into operational taxonomic units and classified utilizing relevant databases. Alpha- and beta-diversity analyses were conducted, along with relative abundance profiling of microbial communities. Our findings revealed similar microbial richness and diversity across studies and determined shifts in microbial community structure determined by periodontitis induction and study of origin. Clear variations in the relative abundance of bacterial taxa were observed starting on day 5 after ligation and onward, consistent with a distinct microbial composition during health and experimental periodontitis. We also uncovered differentially represented bacterial taxa across studies, dominating periodontal health and LIP-associated communities. Collectively, this reanalysis provides a unified overview of microbial dysbiosis during the LIP model, providing new insights that aim to inform further studies dedicated to unraveling oral host-microbial interactions.


Assuntos
Microbiota , Periodontite , Animais , Bactérias/genética , DNA Ribossômico , Disbiose/microbiologia , Camundongos , Microbiota/genética , Periodontite/microbiologia , RNA Ribossômico 16S/genética
9.
Front Cell Infect Microbiol ; 12: 935806, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846769

RESUMO

Chronic inflammation is known to contribute to various human cancers. Porphyromonas gingivalis (P. gingivalis), is a gram-negative oral keystone pathogen that may cause severe periodontitis and expresses several virulence factors to affect the host immune system. Periodontitis is a chronic infectious disease that while progression, may cause loss of attachment and destruction of the tooth supporting tissues. Prostate cancer is one of the most common malignancies in men. Increasing evidence links periodontitis with prostate cancer, however the mechanisms explaining this relationship remain unclear. The aim of this study was to investigate the expression and signaling pathway of programmed death ligand 1 (PD-L1) in a prostate cancer cell line after infection with P. gingivalis and stimulation with P. gingivalis components to reveal the mechanism of tumor-induced immune evasion associated with bacterial infection in the tumor environment. Prostate cancer cells were infected with different concentrations of viable P. gingivalis and treated with different concentrations of heat-killed P. gingivalis and P. gingivalis cell components, including the total membrane fraction, inner membrane fraction, outer membrane fraction, cytosolic fraction and peptidoglycan (PGN). Chemical inhibitors were used to block different important molecules of signaling pathways to assess the participating signal transduction mechanisms. PD-L1 expression was detected by Western blot after 24 h of infection. PD-L1 was demonstrated to be upregulated in prostate cancer cells after infection with viable and with heat-killed P. gingivalis membrane fractions. Also isolated PGN induced PD-L1 up-regulation. The upregulation was mediated by the NOD1/NOD2 signaling pathway. No upregulation could be detected after treatment of the cells with P. gingivalis lipopolysaccharide (LPS). These results indicate, that chronic inflammatory disease can contribute to tumor immune evasion by modifying the tumor microenvironment. Thus, chronic infection possibly plays an essential role in the immune response and may promote the development and progression of prostate cancer.


Assuntos
Periodontite , Neoplasias da Próstata , Antígeno B7-H1/metabolismo , Humanos , Masculino , Periodontite/microbiologia , Porphyromonas gingivalis , Microambiente Tumoral , Regulação para Cima
10.
Artigo em Inglês | MEDLINE | ID: mdl-35805491

RESUMO

(1) Background: Probiotics can be considered a non-invasive periodontal monotherapy for the modulation of microbiota when periodontal treatment is not accessible. The aim was to evaluate the ability of Lactobacillus reuteri Prodentis as monotherapy to modulate periodontal parameters and subgingival biofilm dysbiosis. (2) Methods: A 30-year-old patient with periodontitis was followed longitudinally after one month of daily consumption of L. reuteri Prodentis (T0). Periodontal measurements and microbial identification by Checkerboard DNA-DNA hybridization of 40 bacteria were compared between baseline (T0) and 30 days (T1) or 90 days (T2), using the Kruskal-Wallis (KW) and Mann-Whitney U (MW) tests. (3) Results: Low values of pocket depth, attachment level, dental plaque, gingival erythema (GE), and suppuration were observed at T0 vs. T1, with the clinical improvement of GE (p < 0.05, MW) and the recovery of tooth 46 fistulation. T1 vs. T0 comparisons showed lower levels (Lev) or proportions (Prop) of Parvimonas micra (Lev: p < 0.05, MW; Prop: p < 0.01, MW) and Streptococcus gordonii (Prop: p < 0.05, MW), and a predominance (Lev/Prop) of Actinomyces odontolyticus and Streptococcus mitis; lower levels and proportions of P. micra, Eubacterium saburreum, Porphyromonas gingivalis, and Tannerella forsythia were observed in tooth 46 (T1/T2 vs. T0). (4) Conclusions: Under monotherapy with L. reuteri Prodentis, periodontal measurements of the patient were maintained, with selective changes in the subgingival microbiota that were proportional to the time of probiotic administration, with any additional periodontal treatment.


Assuntos
Lactobacillus reuteri , Periodontite , Probióticos , Adulto , DNA , Disbiose/terapia , Humanos , Periodontite/microbiologia , Periodontite/terapia , Porphyromonas gingivalis , Probióticos/uso terapêutico
11.
Biomolecules ; 12(6)2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35740958

RESUMO

Background: Periodontitis is an inflammatory disease caused by microorganisms involving the supporting tissues of the teeth. Gene variants may influence both the composition of the biofilm in the oral cavity and the host response. The objective of the study was to investigate the potential correlations between the disease susceptibility, the presence and the quantity of periodontopathogenic oral bacterial composition and the VDR gene polymorphisms. Methods: Fifty (50) unrelated periodontal patients and forty-one (41) healthy controls were selected for genomic DNA extraction. DNA concentration was measured and analyzed. The periodontopathogenic bacterial species were identified and quantified using a Real Time PCR performed with species-specific primers and probes. Results: Genotype distribution showed a different distribution between the groups for BsmI rs1544410 genotypes (p = 0.0001) with a prevalence of the G(b) allele in periodontal patients (p = 0.0003). Statistical significance was also found for VDR TaqI rs731236 (p ≤ 0.00001) with a prevalence of the T(T) allele in periodontal patients (p ≤ 0.00001). The average bacterial copy count for the periodontitis group was significantly higher than that of control group. Dividing patients into two groups based on high or low bacterial load, FokI rs2228570 T allele (f) was statistically more represented in patients with high bacterial load. Conclusions: The findings of the study suggest the involvement of the VDR gene BsmI and TaqI polymorphisms in periodontal disease, while FokI and BsmI may be involved in determining an increased presence of periodontopathogens.


Assuntos
Periodontite , Receptores de Calcitriol , Bactérias , Carga Bacteriana , Estudos de Casos e Controles , DNA , Predisposição Genética para Doença , Humanos , Periodontite/genética , Periodontite/microbiologia , Projetos Piloto , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética
12.
J Periodontol ; 93(9): 1421-1433, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35644006

RESUMO

BACKGROUND: Numerous lines of evidence link periodontal pathobionts and their virulence factors with endothelial damage. Most research has been conducted using single species infections at the exclusion of other periodontal microorganisms that have been identified in vascular tissue. Here, we assessed endothelial infection with either single or mixed periodontal species infection and examined their effect on endothelial damage and permeability. METHODS: Cell surface abundance of platelet endothelial cell adhesion molecule-1 (PECAM-1) or endothelial permeability following infection with Porphyromonas gingivalis, Fusobacterium nucleatum subspecies (ssp) nucleatum, ssp polymorphum or Tannerella forsythia as single or mixed species infection was determined by flow cytometry and a fluorescent dextran permeability assay. Zebrafish embryos were infected systemically with either single or mixed species with mortality and disease measured over time. RESULTS: F. nucleatum ssp nucleatum, ssp polymorphum and P. gingivalis significantly reduced PECAM-1 abundance in single species infection, whereas T. forsythia had no effect. F. nucleatum ssp polymorphum caused considerable mortality and morbidity in a zebrafish systemic infection model. Polymicrobial infection underscored the virulence of F. nucleatum ssp polymorphum in particular with increased endothelial cell death and reduced PECAM-1 abundance in co-infection studies with this organism. When injected systemically into zebrafish in polymicrobial infection, fluorescently labeled bacteria were distributed throughout the vasculature and cardiac region where, in some instances, they co-localized with each other. CONCLUSIONS: These data provide further evidence on the effects of F. nucleatum on endothelium adhesion molecule abundance and permeability while also highlighting the importance of performing polymicrobial infection to study the molecular mechanisms associated with periodontal pathogen-induced vascular damage.


Assuntos
Coinfecção , Infecções por Fusobacterium , Periodontite , Animais , Dextranos/farmacologia , Endotélio , Fusobacterium nucleatum , Periodontite/microbiologia , Permeabilidade , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Porphyromonas gingivalis , Fatores de Virulência , Peixe-Zebra
13.
FEMS Microbiol Lett ; 369(1)2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35689660

RESUMO

Patients with Crohn's disease (CD) have higher incidences of oral diseases such as dental caries and periodontitis than healthy people. Studies indicate that the interaction between gut and oral microbiota is an important factor. To compare the composition and diversity of the oral microbiome in periodontitis and CD-associated periodontitis, subgingival plaque and saliva samples from patients with these diseases were collected for 16S rRNA gene sequencing analyses. In CD-associated periodontitis, the subgingival plaque had greater microbial diversity than saliva. Subgingival plaque had decreased abundances of Firmicutes, Streptococcus, and Haemophilus and increased abundances of Bacteroidetes, Actinomyces, Treponema_2, Capnocytophaga, and Porphyromonas relative to saliva. The microbial composition in subgingival plaque was similar between the two diseases. Both red complex (Porphyromonas, Tannerella, and Treponema) and orange complex (Fusobacteria) bacteria were abundant in periodontitis subgingival plaque, while orange complex bacteria (Prevotella_2 and Prevotella) were abundant in CD-associated periodontitis subgingival plaque. Pocket depth was significantly positively correlated with multiple periodontal pathogens, including Porphyromonas, Tannerella, and Treponema. This study reveals the similarities and differences in the oral microbiome between periodontitis and CD-associated periodontitis, which provides a foundation to further explore the associations between CD and periodontitis.


Assuntos
Doença de Crohn , Cárie Dentária , Microbiota , Periodontite , Humanos , Periodontite/microbiologia , Porphyromonas gingivalis/genética , RNA Ribossômico 16S/genética
14.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 57(6): 595-603, 2022 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-35692003

RESUMO

Objective: To study the effects of salivary microbiota in patients with periodontitis on the tryptophan-aryl hydrocarbon receptor (AhR) signaling axis in mice with periodontitis and to provide theoretical basis as well as new ideas for the influences of periodontitis on systemic metabolism. Methods: Salivary microbiota of 12 healthy individuals and 14 patients with periodontitis were collected in Nanjing Stomatological Hospital, Medical School of Nanjing University from June to December of 2020. According to the random number table method, twenty-four mice were randomly divided into three groups: Sham group (control group), P group (periodontitis patients' salivary microbiota group) and H group (periodontal healthy individuals' salivary microbiota group). The maxillary second molars of all mice were treated with silk thread ligation to induce periodontitis. Phosphate buffer as well as salivary microbiota of periodontal healthy individuals and periodontitis patients were gavaged into periodontitis mice for 2 weeks. The expression of inflammatory factors in mice serum were detected by enzyme linked immunosorbent assay, and the expression of tryptophan and indole metabolites in intestinal tract and serum were detected by liquid chromatography-mass spectrometry. The expression of AhR in intestinal tract of mice was detected by immunohistochemistry and quantitative real time-PCR while gut microbiota constitution was detected by 16S rRNA gene sequencing. The remaining saliva samples of periodontitis patients and periodontal healthy individuals were applied to detect the expression of tryptophan and indole metabolites themselves. Results: The salivary microbiota of periodontitis patients could induce the expression of interleukin-1ß [P group: (162.38±39.46) pg/ml, H group: (82.83±20.01) pg/ml; t=4.40, P=0.001) and tumor necrosis factor-α [P group: (361.16±123.90) pg/ml, H group: (191.66±106.87) pg/ml; t=2.54, P=0.030) in serum of periodontitis mice, and reduce the expression of AhR in colon (P group: 1.18±0.05, H group:1.83±0.47; t=3.09, P=0.015) and ileum (P group: 0.80±0.13, H group: 1.18±0.11; t=4.93, P=0.001). After gavage of salivary microbiota of periodontitis patients to the mice, tryptophan (P group: (18.1±3.8)×107, H group: (26.6±6.6)×107; t=2.49, P=0.037] and indole lactic acid [P group: (1.9±0.7)×107, H group: (3.7±0.6)×107; t=4.49, P=0.002) in serum of periodontitis mice were significantly decreased, but was relatively disorder in intestinal tract. However, the expressions of tryptophan and indole metabolites in saliva of periodontitis patients were higher than those of periodontal healthy individuals. There were significant differences in indole propionic acid [P group: (1 239.39±818.72) nmol/L, H group: (56.96±38.33) nmol/L; t=2.83, P=0.022]. What we find noteworthy was that the expressions of indolelactic acid metabolism in saliva, serum and intestinal were consistent, and salivary microbiota of periodontitis patients could reduce the relative abundance of indolelactic acid-producing bacteria in the gut, suggesting that the salivary microbiota of periodontitis patients might affect the expression of AhR through gut microbiota disorder and indolelactic acid downregulation. Conclusions: Salivary microbiota in patients with periodontitis may affect the systemic inflammatory state through down-regulating the expression of tryptophan-AhR signal axis.


Assuntos
Microbiota , Periodontite , Animais , Humanos , Indóis , Camundongos , Periodontite/microbiologia , RNA Ribossômico 16S/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Triptofano/metabolismo
15.
Cell Physiol Biochem ; 56(3): 270-281, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35712829

RESUMO

BACKGROUND/AIMS: Interleukin 33 (IL-33) plays a significant role in immunity but its role in bone physiology and periodontitis needs to be further investigated. The aim of this study was to decipher the contribution of IL-33 to bone homeostasis under physiological conditions, and to alveolar bone loss associated with experimental periodontitis (EP) in IL-33 knockout (KO) mice and their wildtype (WT) littermates. METHODS: The bone phenotype of IL-33 KO mice was studied in the maxilla, femur, and fifth lumbar vertebra by micro-computed tomography (micro-CT). EP was induced by a ligature soaked with the periopathogen Porphyromonas gingivalis (Pg) around a maxillary molar. Alveolar bone loss was quantified by micro-CT. The resorption parameters were assessed via toluidine blue staining on maxillary sections. In vitro osteoclastic differentiation assays using bone marrow cells were performed with or without lipopolysaccharide from Pg (LPS-Pg). RESULTS: First, we showed that under physiological conditions, IL-33 deficiency increased the trabecular bone volume/total volume ratio (BV/TV) of the maxillary bone in male and female mice, but not in the femur and fifth lumbar vertebra, suggesting an osteoprotective role for IL-33 in a site-dependent manner. The severity of EP induced by Pg-soaked ligature was increased in IL-33 KO mice but in female mice only, through an increase in the number of osteoclasts. Moreover, osteoclastic differentiation from bone marrow osteoclast progenitors in IL-33-deficient female mice is enhanced in the presence of LPS-Pg. CONCLUSION: Taken together, our data demonstrate that IL-33 plays a sex-dependent osteoprotective role both under physiological conditions and in EP with Pg.


Assuntos
Perda do Osso Alveolar , Interleucina-33 , Periodontite , Perda do Osso Alveolar/microbiologia , Animais , Feminino , Interleucina-33/deficiência , Interleucina-33/genética , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Knockout , Osteoclastos , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , Microtomografia por Raio-X
16.
J Clin Periodontol ; 49(9): 922-931, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35713232

RESUMO

AIM: To explore the immunological defensive effects of platelets on periodontal pathogens in the gingival crevicular fluid (GCF). MATERIALS AND METHODS: GCF samples were collected from 20 patients with periodontitis and 10 healthy controls. Platelets in the GCF were detected by immunocytochemistry and immunofluorescence. Isolated platelets from healthy volunteers were co-cultured with Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn). The interactions between platelets and periodontal pathogens were observed by transmission and scanning electron microscopy. The isolated platelets plus neutrophils were co-cultured with Pg or Fn, and the formation of neutrophil extracellular traps (NETs) was evaluated by staining with Sytox Green. RESULTS: The platelet level in the GCF was higher in patients with periodontitis than in healthy controls. Platelets interacted with bacteria and neutrophils in the GCF. In vitro, platelets recruited and engulfed periodontal pathogens. In response to periodontal pathogens, neutrophils released web chromatin, and platelets promoted the formation of intensive NETs. CONCLUSIONS: Platelets, migrating to the gingival sulcus, may exert direct antibacterial effects or assist neutrophils.


Assuntos
Líquido do Sulco Gengival , Periodontite , Plaquetas , Fusobacterium nucleatum , Humanos , Periodontite/microbiologia , Porphyromonas gingivalis
17.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 57(6): 648-653, 2022 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-35692011

RESUMO

The oral cavity is the second largest microbial habitat in the whole body. Due to the divergence of oxygen, metabolic substrates and rate-limiting enzymes, oral bacteria are classified into sugar-metabolizing and nitrogen-compound-metabolizing bacteria according to their metabolic characteristics. The metabolites include organic acids, carbon dioxide, amino acids, proteins, and ammonia. Oral bacterial metabolites are very important for oral bacteria growth and reproduction, and also play an important role in systemic diseases such as periodontitis, oral cancer, intestinal diseases, diabetes and atherosclerosis. Therefore, in-depth exploration of oral bacterial metabolism is of great significance to understand the impact of oral cavity on systemic health. This article reviews the metabolic characteristics of oral bacteria and their correlation with systemic diseases.


Assuntos
Microbiota , Periodontite , Bactérias , Humanos , Periodontite/microbiologia
18.
Int J Mol Sci ; 23(9)2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35563501

RESUMO

Periodontitis (PD) is a polymicrobial dysbiotic immuno-inflammatory disease. It is more prevalent in males and has poorly understood pathogenic molecular mechanisms. Our primary objective was to characterize alterations in sex-specific microRNA (miRNA, miR) after periodontal bacterial infection. Using partial human mouth microbes (PAHMM) (Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) in an ecological time-sequential polybacterial periodontal infection (ETSPPI) mouse model, we evaluated differential mandibular miRNA profiles by using high-throughput Nanostring nCounter® miRNA expression panels. All PAHMM mice showed bacterial colonization (100%) in the gingival surface, an increase in alveolar bone resorption (p < 0.0001), and the induction of a specific immunoglobin G antibody immune response (p < 0.001). Sex-specific differences in distal organ bacterial dissemination were observed in the heart (82% male vs. 28% female) and lungs (2% male vs. 68% female). Moreover, sex-specific differential expression (DE) of miRNA was identified in PAHMM mice. Out of 378 differentially expressed miRNAs, we identified seven miRNAs (miR-9, miR-148a, miR-669a, miR-199a-3p, miR-1274a, miR-377, and miR-690) in both sexes that may be implicated in the pathogenesis of periodontitis. A strong relationship was found between male-specific miR-377 upregulation and bacterial dissemination to the heart. This study demonstrates sex-specific differences in bacterial dissemination and in miRNA differential expression. A novel PAHMM mouse and ETSPPI model that replicates human pathobiology can be used to identify miRNA biomarkers in periodontitis.


Assuntos
Perda do Osso Alveolar , MicroRNAs , Periodontite , Animais , Feminino , Humanos , Masculino , Camundongos , MicroRNAs/genética , Periodontite/microbiologia , Porphyromonas gingivalis , Treponema denticola/genética
19.
Nutrients ; 14(10)2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35631266

RESUMO

Probiotics have aroused increasing concern as an intervention strategy for periodontitis (PD), but their underlying mechanism of action remains poorly characterized. Regarding the significance of oral microbiota dysbiosis related to PD, we predicted that the preventive activity of probiotics may be influenced by suppressing the bacterial pathogenicity. Herein, we investigated the effects of Lactobacillus paracasei L9 (L9) and Bifidobacterium animalis A6 (A6) on PD using a rat model, and demonstrated a regulatory effect of probiotics on oral flora from a metagenomics perspective. Oral administration of A6 or L9 effectively relieved gingival bleeding, periodontal inflammatory infiltration, and alveolar bone resorption. In addition, A6 or L9 treatment reduced the inflammatory response and increased the expression of anti-inflammatory cytokines, which we expected to ameliorate alveolar bone resorption as mediated by the receptor activator of the nuclear factor-κB ligand/OPG signaling pathway. More importantly, using metagenomic sequencing, we showed that probiotics significantly altered the taxonomic composition of the subgingival microbiome, and reduced the relative proportions of pathogenic bacterial genera such as Streptococcus, Fusobacterium, Veillonella, and Escherichia. Both probiotics significantly inhibited levels of bacterial virulence factors related to adherence, invasion, exoenzyme, and complement protease functions that are strongly correlated with the pathogenesis of PD. Our overall results suggest that A6 and L9 may constitute promising prophylactic agents for PD, and should thus be further explored in the future.


Assuntos
Perda do Osso Alveolar , Bifidobacterium animalis , Lactobacillus paracasei , Periodontite , Animais , Bactérias , Metagenômica , Periodontite/microbiologia , Periodontite/terapia , Ratos
20.
Gut Microbes ; 14(1): 2073785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35549648

RESUMO

Intratumor microbiome shapes the immune system and influences the outcome of various tumors. Porphyromonas gingivalis (P. gingivalis), the keystone periodontal pathogen, is highly epidemically connected with pancreatic cancer (PC). However, its causative role and the underlining mechanism in promoting PC oncogenesis remain unclear. Here, we illustrated the landscape of intratumor microbiome and its bacterial correlation with oral cavity in PC patients, where P. gingivalis presented both in the oral cavity and tumor tissues. When exposed to P. gingivalis, tumor development was accelerated in orthotopic and subcutaneous PC mouse model, and the cancerous pancreas exhibited a neutrophils-dominated proinflammatory tumor microenvironment. Mechanistically, the intratumoral P. gingivalis promoted PC progression via elevating the secretion of neutrophilic chemokines and neutrophil elastase (NE). Collectively, our study disclosed the bacterial link between periodontitis and PC, and revealed a previously unrecognized mechanism of P. gingivalis in PC pathophysiology, hinting at therapeutic implications.


Assuntos
Microbioma Gastrointestinal , Periodontite , Animais , Carcinogênese , Transformação Celular Neoplásica , Humanos , Elastase de Leucócito , Camundongos , Neutrófilos , Pâncreas , Periodontite/microbiologia , Porphyromonas gingivalis , Microambiente Tumoral
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