Subgingival Microbiome in Rheumatoid Arthritis Patients with Periodontitis.
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ABSTRACT:
SUBMITTER: Chen YJ
PROVIDER: S-EPMC9456296 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Subgingival Microbiome in Rheumatoid Arthritis Patients with Periodontitis.
Chen Yi-Jing YJ Hung Wei-Chun WC Chou Yu-Hsiang YH Lai Chern-Hsiung CH Peng Po P Jhou Pei-Syuan PS Tsai Min-Ru MR Sheu Jim Jinn-Chyuan JJ Yen Jeng-Hsien JH
International journal of molecular sciences 20220831 17
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 rR ...[more]
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Project description:ObjectiveRheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that share common risk factors. However, the bidirectional relationship between RA and periodontal disease is not fully understood. This study was undertaken to describe the bacterial component of the subgingival microbiome in RA patients and to relate this to RA disease activity and periodontal status.MethodsPatients with chronic established RA (N = 78) were periodontally examined and their subgingival plaque samples were collected; their clinical and laboratory data on RA status and medication were obtained from medical records. Bacterial DNA was quantified by universal 16S rDNA qPCR, and Porphyromonas gingivalis by species-specific qPCR. For microbiome assessment, 16S rDNA amplicon sequencing was performed.ResultsActive RA was diagnosed in 58% of the patients and periodontitis in 82% (mild: 9%, moderate: 55%, severe: 18%). P. gingivalis was present in 14% of the samples. Different levels of gingival bleeding, periodontal probing depth, RA disease status, prednisolone use and smoking were associated with significantly different microbiome compositions. Two subgingival microbial community types were discerned.ConclusionIn RA patients with active disease, anti-inflammatory medication as part of RA therapy was associated with better oral health status and a healthier subgingival microbiome compared to that of RA patients in remission, especially those in remission who were current smokers. RA patients in remission with current smoking status may particularly benefit from a systematic periodontal treatment program. The potential role of microbial community types in patient stratification and personalized therapy should be assessed in longitudinal studies.
| S-EPMC6145512 | biostudies-literature
Project description:To describe the subgingival microbiome of individuals with Down syndrome (DS). We conducted a cross-sectional observational study that obtained bacterial DNA samples from 50 patients with DS, 25 with periodontitis (PDS) and 25 with a healthy periodontal condition (HDS). The samples were analyzed by sequencing the 16S rRNA gene V3-V4 hypervariable region using the MiSeq System. Taxonomic affiliations were assigned using the naïve Bayesian classifier integrated in QIIME2 plugins. We evaluated the difference in bacteria abundance between the sample groups using Wilcoxon and Kruskal-Wallis tests. We evaluated the alpha diversity of the identified species using the Observed, Chao1metric, ACE and Shannon indices and evaluated beta diversity with principal coordinate analysis (registration code: 2018/510). Twenty-one genera and 39 bacterial species showed a significantly different abundance between the study groups. Among the genera, Porphyromonas, Treponema, Tannerella and Aggregatibacter were more abundant in the PDS group than in the HDS group, as were the less commonly studied Filifactor, Fretibacterium and Desulfobulbus genera. Among the species, Porphyromonas spp. and Tannerella spp. were the most abundant in the PDS group; the most abundant species in the HDS group were Pseudomonas spp., Granulicatella spp. and Gemella spp. Well-recognized periodontal pathogens and newly proposed pathogenic taxa were associated with periodontitis in patients with DS.
| S-EPMC7463899 | biostudies-literature
Project description:BackgroundSubgingival microbiome in disease-associated subgingival sites is known to be dysbiotic and significantly altered. In patients with rheumatoid arthritis (RA), the extent of dysbiosis in disease- and health-associated subgingival sites is not clear.Methods8 RA and 10 non-RA subjects were recruited for this pilot study. All subjects received full oral examination and underwent collection of subgingival plaque samples from both shallow (periodontal health-associated, probing depth ≤ 3mm) and deep subgingival sites (periodontal disease-associated, probing depth ≥ 4 mm). RA subjects also had rheumatological evaluation. Plaque community profiles were analyzed using 16 S rRNA sequencing.ResultsThe phylogenetic diversity of microbial communities in both RA and non-RA controls was significantly higher in deep subgingival sites compared to shallow sites (p = 0.022), and the overall subgingival microbiome clustered primarily according to probing depth (i.e. shallow versus deep sites), and not separated by RA status. While a large number of differentially abundant taxa and gene functions was observed between deep and shallow sites as expected in non-RA controls, we found very few differentially abundant taxa and gene functions between deep and shallow sites in RA subjects. In addition, compared to non-RA controls, the UniFrac distances between deep and shallow sites in RA subjects were smaller, suggesting increased similarity between deep and shallow subgingival microbiome in RA. Streptococcus parasanguinis and Actinomyces meyeri were overabundant in RA subjects, while Gemella morbillorum, Kingella denitrificans, Prevotella melaninogenica and Leptotrichia spp. were more abundant in non-RA subjects.ConclusionsThe aggregate subgingival microbiome was not significantly different between individuals with and without rheumatoid arthritis. Although the differences in the overall subgingival microbiome was driven primarily by probing depth, in contrast to the substantial microbiome differences typically seen between deep and shallow sites in non-RA patients, the microbiome of deep and shallow sites in RA patients were more similar to each other. These results suggest that factors associated with RA may modulate the ecology of subgingival microbiome and its relationship to periodontal disease, the basis of which remains unknown but warrants further investigation.
| S-EPMC8105973 | biostudies-literature
Project description:ObjectiveStudies that demonstrate an association between rheumatoid arthritis (RA) and dysbiotic oral microbiomes are often confounded by the presence of extensive periodontitis in these individuals. This study was undertaken to investigate the role of RA in modulating the periodontal microbiome by comparing periodontally healthy individuals with RA to those without RA.MethodsSubgingival plaque was collected from periodontally healthy individuals (22 with RA and 19 without RA), and the 16S gene was sequenced on an Illumina MiSeq platform. Bacterial biodiversity and co-occurrence patterns were examined using the QIIME and PhyloToAST pipelines.ResultsThe subgingival microbiomes differed significantly between patients with RA and controls based on both community membership and the abundance of lineages, with 41.9% of the community differing in abundance and 19% in membership. In contrast to the sparse and predominantly congeneric co-occurrence networks seen in controls, RA patients revealed a highly connected grid containing a large intergeneric hub anchored by known periodontal pathogens. Predictive metagenomic analysis (PICRUSt) demonstrated that arachidonic acid and ester lipid metabolism pathways might partly explain the robustness of this clustering. As expected from a periodontally healthy cohort, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were not significantly different between groups; however, Cryptobacterium curtum, another organism capable of producing large amounts of citrulline, emerged as a robust discriminant of the microbiome in individuals with RA.ConclusionOur data demonstrate that the oral microbiome in RA is enriched for inflammophilic and citrulline-producing organisms, which may play a role in the production of autoantigenic citrullinated peptides in RA.
| S-EPMC6019644 | biostudies-literature
Project description:BackgroundAlthough localized aggressive periodontitis (LAP), generalized aggressive periodontitis (GAP), and chronic periodontitis (CP) are microbially driven diseases, our inability to separate disease-specific associations from those common to all three forms of periodontitis has hampered biomarker discovery. Therefore, we aimed to map the genomic content of, and the biological pathways encoded by, the microbiomes associated with these clinical phenotypes. We also estimated the extent to which these biomes are governed by the Anna Karenina principle (AKP), which states that eubiotic communities are similar between individuals while disease-associated communities are highly individualized.MethodsWe collected subgingival plaque from 25 periodontally healthy individuals and diseased sites of 59 subjects with stage 3 periodontitis and used shotgun metagenomics to characterize the aggregate of bacterial genes.ResultsBeta-dispersion metrics demonstrated that AKP was most evident in CP, followed by GAP and LAP. We discovered broad dysbiotic signatures spanning the three phenotypes, with over-representation of pathways that facilitate life in an oxygen-poor, protein- and heme-rich, pro-oxidant environment and enhance capacity for attachment and biofilm formation. Phenotype-specific indicators were more readily evident in LAP microbiome than GAP or CP. Genes that enable acetate-scavenging lifestyle, utilization of alternative nutritional sources, oxidative and nitrosative stress responses, and siderophore production were unique to LAP. An attenuation of virulence-related functionalities and stress response from LAP to GAP to CP was apparent. We also discovered that clinical phenotypes of disease resolved variance in the microbiome with greater clarity than the newly established grading system. Importantly, we observed that one third of the metagenome of LAP is unique to this phenotype while GAP shares significant functional and taxonomic features with both LAP and CP, suggesting either attenuation of an aggressive disease or an early-onset chronic disease.ConclusionWithin the limitations of a small sample size and a cross-sectional study design, the distinctive features of the microbiomes associated with LAP and CP strongly persuade us that these are discrete disease entities, while calling into question whether GAP is a separate disease, or an artifact induced by cross-sectional study designs. Further studies on phenotype-specific microbial genes are warranted to explicate their role in disease etiology. Video Abstract.
| S-EPMC8091542 | biostudies-literature
Project description:ObjectiveTo examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.MethodsPatients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression.ResultsPresence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection.ConclusionBoth PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.
| S-EPMC4115329 | biostudies-literature
Project description:Since periodontitis and type 2 diabetes mellitus are complex diseases, a thorough understanding of their pathogenesis requires knowing the relationship of these pathologies with other disorders and environmental factors. In this study, the representability of the subgingival periodontal microbiome of 46 subjects was studied by 16S rRNA gene sequencing and shotgun sequencing of pooled samples. We examined 15 patients with chronic periodontitis (CP), 15 patients with chronic periodontitis associated with type 2 diabetes mellitus (CPT2DM), and 16 healthy subjects (Control). The severity of generalized chronic periodontitis in both periodontitis groups of patients (CP and CPT2DM) was moderate (stage II). The male to female ratios were approximately equal in each group (22 males and 24 females); the average age of the subjects was 53.9 ± 7.3 and 54.3 ± 7.2 years, respectively. The presence of overweight patients (Body Mass Index (BMI) 30-34.9 kg/m2) and patients with class 1-2 obesity (BMI 35-45.9 kg/m2) was significantly higher in the CPT2DM group than in patients having only chronic periodontitis or in the Control group. However, there was no statistically significant difference in all clinical indices between the CP and CPT2DM groups. An analysis of the metagenomic data revealed that the alpha diversity in the CPT2DM group was increased compared to that in the CP and Control groups. The microbiome biomarkers associated with experimental groups were evaluated. In both groups of patients with periodontitis, the relative abundance of Porphyromonadaceae was increased compared to that in the Control group. The CPT2DM group was characterized by a lower relative abundance of Streptococcaceae/Pasteurellaceae and a higher abundance of Leptotrichiaceae compared to those in the CP and Control groups. Furthermore, the CP and CPT2DM groups differed in terms of the relative abundance of Veillonellaceae (which was decreased in the CPT2DM group compared to CP) and Neisseriaceae (which was increased in the CPT2DM group compared to CP). In addition, differences in bacterial content were identified by a combination of shotgun sequencing of pooled samples and genome-resolved metagenomics. The results indicate that there are subgingival microbiome-specific features in patients with chronic periodontitis associated with type 2 diabetes mellitus.
| S-EPMC8145315 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is a systemic disease, predisposing patients to other inflammatory conditions including periodontitis. The subgingival microbiome, a key player in periodontitis pathogenesis, is not well characterized in T2DM population. To better understand whether the subgingival microbiome is different between T2DM and systemically healthy, nondiabetic (ND) subjects, we performed a longitudinal analysis of the subgingival microbiome in T2DM patients (n = 15) compared with ND subjects (n = 16). Using metagenomic shotgun sequencing, we investigated the microbiome in the healthy periodontal state, periodontitis state, and resolved state after treatment. We found that in the periodontitis state, the shift in the subgingival microbiome from the healthy state was less prominent in T2DM compared with ND subjects, yet the clinical signs of disease were similar for both. Furthermore, we revealed highly correlated presence of pathogenic species in relative abundance not only in the periodontitis state, but also in the healthy state in T2DM, suggesting an elevated risk of progression to periodontitis in this cohort. We further investigated the functional potentials of the subgingival microbiome and identified a set of microbial marker genes associated with the clinical states. These genes were significantly enriched in 21 pathways, some of which are associated with periodontitis and some potentially link T2DM and periodontitis. This study identified the longitudinal changes of the subgingival microbiome associated with periodontitis in T2DM and suggests that T2DM patients are more susceptible to shifts in the subgingival microbiome toward dysbiosis, potentially due to impaired host metabolic and immune regulation.
| S-EPMC6976570 | biostudies-literature
Project description:ObjectiveThe aim of this work was to explore the association between Aggregatibacter actinomycetemcomitans (A actinomycetemcomitans) infection and disease activity amongst those with rheumatoid arthritis (RA) with or without periodontitis (PD) in a Chinese population.MethodsA case-control study was conducted from November 2017 to March 2019. The correlation coefficients between A actinomycetemcomitans positivity and RA-related examination indicators as well as periodontal examination parameters were calculated by using the Spearman correlation analysis.ResultsA total of 115 patients with RA were recruited: 67 patients with RA only and 48 with RA + PD. The percentage of A actinomycetemcomitans positivity was significantly higher in the RA + PD group compared with the RA-only group (P = .007 for positive percentage; P = .020 for percentage of A actinomycetemcomitans positivity in the total oral microbiome). Furthermore, RA-related measures such as Disease Activity Score 28, rheumatoid factor, anticyclic citrullinated peptide, and anticitrullinated protein antibodies were all positively correlated with the percentage of A actinomycetemcomitans positivity (P range: .002∼.041). In addition, significant correlations were observed amongst A actinomycetemcomitans positivity and probing pocket depth (P = .027) and gingival index (P = .043), whereas null correlations were found amongst the percentage of A actinomycetemcomitans positivity and plaque index (P = .344), clinical attachment loss (P = .217), and bleeding on probing (P = .710).ConclusionsA actinomycetemcomitans infection may be related to the development of PD amongst patients with RA.
| S-EPMC10829364 | biostudies-literature
Project description:Chronic periodontitis is an inflammatory disease of the periodontium affecting nearly 65 million adults in the United States. Changes in subgingival microbiota have long been associated with chronic periodontitis. Recent culture-independent molecular studies have revealed the immense richness and complexity of oral microbial communities. However, data sets across studies have not been directly compared, and whether the observed microbial variations are consistent across different studies is not known. Here, we used 16S rRNA sequencing to survey the subgingival microbiota in 25 subjects with chronic periodontal disease and 25 healthy controls and compared our data sets with those of three previously reported microbiome studies. Consistent with data from previous studies, our results demonstrate a significantly altered microbial community structure with decreased heterogeneity in periodontal disease. Comparison with data from three previously reported studies revealed that subgingival microbiota clustered by study. However, differences between periodontal health and disease were larger than the technical variations across studies. Using a prediction score and applying five different distance metrics, we observed two predominant clusters. One cluster was driven by Fusobacterium and Porphyromonas and was associated with clinically apparent periodontitis, and the second cluster was dominated by Rothia and Streptococcus in the majority of healthy sites. The predicted functional capabilities of the periodontitis microbiome were significantly altered. Genes involved in bacterial motility, energy metabolism, and lipopolysaccharide biosynthesis were overrepresented in periodontal disease, whereas genes associated with transporters, the phosphotransferase system, transcription factors, amino acid biosynthesis, and glycolysis/gluconeogenesis were enriched in healthy controls. These results demonstrate significant alterations in microbial composition and function in periodontitis and suggest genes and metabolic pathways associated with periodontal disease.
| S-EPMC4277562 | biostudies-literature