scholarly journals Oral microbial dysbiosis linked to worsened periodontal condition in rheumatoid arthritis patients

2018 ◽  
Author(s):  
Jôice Dias Corrêa ◽  
Gabriel R. Fernandes ◽  
Débora Cerqueira Calderaro ◽  
Santuza Maria Souza Mendonça ◽  
Janine Mayra Silva ◽  
...  

AbstractRheumatoid arthritis (RA) is an autoimmune disorder associated with increased periodontal destruction. It is thought that RA increases the risk of periodontal disease; it is not known how it influences the oral microbiota. Our aim was to analyze the impact of RA on subgingival microbiota and its association with periodontal inflammation and RA activity. Forty-two patients with RA were compared to 47 control subjects without RA. Patients were screened for probing depth, clinical attachment level, bleeding on probing and classified as with or without periodontitis. Subgingival plaque was examined by Illumina MiSeq Sequencing of 16S rRNA gene V4 region and inflammatory cytokines were measured in saliva. RA was associated to severe periodontal disease. In addition, the severity of RA, reflected by the number of tender and swollen joints, was significantly correlated with the presence of pathogenic oral bacteria (i.e. Fusobacterium nucleatum and Treponema socransky). Non-periodontitis RA patients compared to healthy controls had increased microbial diversity and bacterial load, higher levels of pathogenic species (Prevotella, Selenomonas, Anaeroglobus geminatus, Parvimonas micra, Aggregatibacter actinomycetemcomitans) and reduction of health-related species (Streptococcus, Rothia aeria, Kingela oralis). Genes involved with bacterial virulence (i.e. lipopolysaccharide biosynthesis, peptidases) were more prevalent in the subgingival metagenome of subjects with RA. In addition, the degree of oral inflammation reflected by IL-2, IL-6, TNF-α, IFN-γ salivary levels was increased in non-periodontitis RA patients in comparison with controls. Our findings support the hypothesis that RA triggers dysbiosis of subgingival microbiota, which may contribute to worsening periodontal status.Author SummaryRheumatoid arthritis (RA) is an autoimmune disease characterized by joints inflammation, swelling, pain and stiffness. Exactly what starts this disease is still unclear. Some recent studies have suggested mucosal surfaces in the body, like those in the gums, could affect the disease process. It has been observed that people with RA have higher risk of periodontitis (a bacterial inflammatory disease of the gums), compared with the general population, and this may be the start of the autoimmune process. Also, periodontitis increases the severity of RA while interventions by treating periodontitis can improve the symptoms of RA. One of the possible mechanisms that link the higher prevalence of periodontitis in RA patients is the dysbiosis of the oral microbiota triggered by the chronic inflammation in RA. Increased levels of molecules of inflammation may affect the oral environment and change the type of bacteria that live there. Here, we examined RA patients and healthy subjects, screening their oral health and inflammatory markers. We collected their saliva and the dental plaque from the space between the teeth and the gum. We found that RA patients exhibited severe periodontitis, increased levels of inflammatory mediators on their saliva and distinct bacterial communities, with higher proportions of bacteria species linked to periodontal disease, even in patients without periodontitis. We also found that the presence of these bacteria species was linked to worse RA conditions. Our study provides new insights to understand the bi-directional mechanisms linking periodontal disease to the development of RA, showing that we need to pay attention to the oral cavity in patients with RA and refer people for dental evaluation. This practice might have a positive impact in the course of RA.

2021 ◽  
Vol 9 (8) ◽  
pp. 1657
Author(s):  
Anders Esberg ◽  
Linda Johansson ◽  
Ingegerd Johansson ◽  
Solbritt Rantapää Dahlqvist

Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease, and single periodontitis-associated bacteria have been suggested in disease manifestation. Here, the oral microbiota was characterized in relation to the early onset of RA (eRA) taking periodontal status into consideration. 16S rRNA gene amplicon sequencing of saliva bacterial DNA from 61 eRA patients without disease-modifying anti-rheumatic drugs and 59 matched controls was performed. Taxonomic classification at 98.5% was conducted against the Human Oral Microbiome Database, microbiota functions were predicted using PICRUSt, and periodontal status linked from the Swedish quality register for clinically assessed caries and periodontitis. The participants were classified into three distinct microbiota-based cluster groups with cluster allocation differences by eRA status. Independently of periodontal status, eRA patients had enriched levels of Prevotella pleuritidis, Treponema denticola, Porphyromonas endodontalis and Filifactor alocis species and in the Porphyromonas and Fusobacterium genera and functions linked to ornithine metabolism, glucosylceramidase, beta-lactamase resistance, biphenyl degradation, fatty acid metabolism and 17-beta-estradiol-17-dehydrogenase metabolism. The results support a deviating oral microbiota composition already in eRA patients compared with healthy controls and highlight a panel of oral bacteria that may be useful in eRA risk assessment in both periodontally healthy and diseased persons.


2021 ◽  
Vol 43 (3) ◽  
pp. 1460-1472
Author(s):  
Vivianne Cruz de Jesus ◽  
Manu Singh ◽  
Robert J. Schroth ◽  
Prashen Chelikani ◽  
Carol A. Hitchon

The association of taste genetics and the oral microbiome in autoimmune diseases such as rheumatoid arthritis (RA) has not been reported. We explored a novel oral mucosal innate immune pathway involving the bitter taste G protein-coupled receptor T2R38. This case–control study aimed to evaluate whether T2R38 polymorphisms associate with the buccal microbial composition in RA. Genomic DNA was obtained from buccal swabs of 35 RA patients and 64 non-RA controls. TAS2R38 genotypes were determined by Sanger sequencing. The buccal microbiome was assessed by Illumina MiSeq sequencing of the V4-16S rRNA gene. Bacterial community differences were analyzed with alpha and beta diversity measures. Linear discriminant analysis effect size identified taxa discriminating between RA versus non-RA and across TAS2R38 genotypes. TAS2R38 genotype frequency was similar between RA and non-RA controls (PAV/PAV; PAV/AVI; AVI/AVI: RA 42.9%; 45.7%; 11.4% versus controls 32.8%; 48.4%; 18.8%, chi-square (2, N = 99) = 2.1, p = 0.35). The relative abundance of Porphyromonas, among others, differed between RA and non-RA controls. The relative abundance of several bacterial species also differed across TAS2R38 genotypes. These findings suggest an association between T2R38 polymorphisms and RA buccal microbial composition. However, further research is needed to understand the impact of T2R38 in oral health and RA development.


Author(s):  
Ciro Gargiulo Isacco ◽  
Andrea Ballini ◽  
Danila De Vito ◽  
Kieu Cao Diem Nguyen ◽  
Stefania Cantore ◽  
...  

: The current treatment and prevention of oral disorders follow a very sectoral control and procedures considering mouth and its structures as system completely independent from the rest of the body. The main therapeutic approach is carried out on just to keep the levels of oral bacteria and hygiene in an acceptable range compatible with one-way vision of oral-mouth health completely separated from a systemic microbial homeostasis (eubiosis vs dysbiosis). This can negatively impact on the diagnosis of more complex systemic disease and its progression. Dysbiosis is consequence of oral and gut microbiota unbalance with consequences, as reported in current literature, in cardio vascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer’s disease. Likewise, there is the need to highlight and develop a novel philosophical approach in the treatments for oral diseases that will necessarily involve non-conventional approaches.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Relvas ◽  
A. Regueira-Iglesias ◽  
C. Balsa-Castro ◽  
F. Salazar ◽  
J. J. Pacheco ◽  
...  

AbstractThe present study used 16S rRNA gene amplicon sequencing to assess the impact on salivary microbiome of different grades of dental and periodontal disease and the combination of both (hereinafter referred to as oral disease), in terms of bacterial diversity, co-occurrence network patterns and predictive models. Our scale of overall oral health was used to produce a convenience sample of 81 patients from 270 who were initially recruited. Saliva samples were collected from each participant. Sequencing was performed in Illumina MiSeq with 2 × 300 bp reads, while the raw reads were processed according to the Mothur pipeline. The statistical analysis of the 16S rDNA sequencing data at the species level was conducted using the phyloseq, DESeq2, Microbiome, SpiecEasi, igraph, MixOmics packages. The simultaneous presence of dental and periodontal pathology has a potentiating effect on the richness and diversity of the salivary microbiota. The structure of the bacterial community in oral health differs from that present in dental, periodontal or oral disease, especially in high grades. Supragingival dental parameters influence the microbiota’s abundance more than subgingival periodontal parameters, with the former making a greater contribution to the impact that oral health has on the salivary microbiome. The possible keystone OTUs are different in the oral health and disease, and even these vary between dental and periodontal disease: half of them belongs to the core microbiome and are independent of the abundance parameters. The salivary microbiome, involving a considerable number of OTUs, shows an excellent discriminatory potential for distinguishing different grades of dental, periodontal or oral disease; considering the number of predictive OTUs, the best model is that which predicts the combined dental and periodontal status.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christine Drengenes ◽  
Tomas M. L. Eagan ◽  
Ingvild Haaland ◽  
Harald G. Wiker ◽  
Rune Nielsen

Abstract Background Studies on the airway microbiome have been performed using a wide range of laboratory protocols for high-throughput sequencing of the bacterial 16S ribosomal RNA (16S rRNA) gene. We sought to determine the impact of number of polymerase chain reaction (PCR) steps (1- or 2- steps) and choice of target marker gene region (V3 V4 and V4) on the presentation of the upper and lower airway microbiome. Our analyses included lllumina MiSeq sequencing following three setups: Setup 1 (2-step PCR; V3 V4 region), Setup 2 (2-step PCR; V4 region), Setup 3 (1-step PCR; V4 region). Samples included oral wash, protected specimen brushes and protected bronchoalveolar lavage (healthy and obstructive lung disease), and negative controls. Results The number of sequences and amplicon sequence variants (ASV) decreased in order setup1 > setup2 > setup3. This trend appeared to be associated with an increased taxonomic resolution when sequencing the V3 V4 region (setup 1) and an increased number of small ASVs in setups 1 and 2. The latter was considered a result of contamination in the two-step PCR protocols as well as sequencing across multiple runs (setup 1). Although genera Streptococcus, Prevotella, Veillonella and Rothia dominated, differences in relative abundance were observed across all setups. Analyses of beta-diversity revealed that while oral wash samples (high biomass) clustered together regardless of number of PCR steps, samples from the lungs (low biomass) separated. The removal of contaminants identified using the Decontam package in R, did not resolve differences in results between sequencing setups. Conclusions Differences in number of PCR steps will have an impact of final bacterial community descriptions, and more so for samples of low bacterial load. Our findings could not be explained by differences in contamination levels alone, and more research is needed to understand how variations in PCR-setups and reagents may be contributing to the observed protocol bias.


2021 ◽  
Author(s):  
Alba Regueira-Iglesias ◽  
Lara Vazquez-Gonzalez ◽  
Carlos Balsa-Castro ◽  
Triana Blanco-Pintos ◽  
Victor Manuel Arce ◽  
...  

This in silico investigation aimed to: 1) evaluate a set of primer pairs with high coverage, including those most commonly used in the literature, to find the different oral species with 16S rRNA gene amplicon similarity/identity (ASI) values ≥97%; and 2) identify oral species that may be erroneously clustered in the same operational taxonomic unit (OTU) and ascertain whether they belong to distinct genera or other higher taxonomic ranks. Thirty-nine primer pairs were employed to obtain amplicon sequence variants (ASVs) from the complete genomes of 186 bacterial and 135 archaeal species. For each primer, ASVs without mismatches were aligned using BLASTN and their similarity values were obtained. Finally, we selected ASVs from different species with an ASI value ≥97% that were covered 100% by the query sequences. For each primer, the percentage of species-level coverage with no ASI≥97% (SC-NASI≥97%) was calculated. Based on the SC-NASI≥97% values, the best primer pairs were OP_F053-KP_R020 for bacteria (65.05%), KP_F018-KP_R002 for archaea (51.11%), and OP_F114-KP_R031 for bacteria and archaea together (52.02%). Eighty percent of the oral-bacteria and oral-archaea species shared an ASI≥97% with at least one other taxa, including Campylobacter, Rothia, Streptococcus, and Tannerella, which played conflicting roles in the oral microbiota. Moreover, around a quarter and a third of these two-by-two similarity relationships were between species from different bacteria and archaea genera, respectively. Furthermore, even taxa from distinct families, orders, and classes could be grouped in the same cluster. Consequently, irrespective of the primer pair used, OTUs constructed with a 97% similarity provide an inaccurate description of oral-bacterial and oral-archaeal species, greatly affecting microbial diversity parameters. As a result, clustering by OTUs impacts the credibility of the associations between some oral species and certain health and disease conditions. This limits significantly the comparability of the microbial diversity findings reported in oral microbiome literature.


2022 ◽  
Vol 23 (2) ◽  
pp. 846
Author(s):  
Stanislas Martin ◽  
Audrey Foulon ◽  
Wissam El Hage ◽  
Diane Dufour-Rainfray ◽  
Frédéric Denis

The study aimed to examine the impact of the oropharyngeal microbiome in the pathophysiology of schizophrenia and to clarify whether there might be a bidirectional link between the oral microbiota and the brain in a context of dysbiosis-related neuroinflammation. We selected nine articles including three systemic reviews with several articles from the same research team. Different themes emerged, which we grouped into 5 distinct parts concerning the oropharyngeal phageome, the oropharyngeal microbiome, the salivary microbiome and periodontal disease potentially associated with schizophrenia, and the impact of drugs on the microbiome and schizophrenia. We pointed out the presence of phageoma in patients suffering from schizophrenia and that periodontal disease reinforces the role of inflammation in the pathophysiology of schizophrenia. Moreover, saliva could be an interesting substrate to characterize the different stages of schizophrenia. However, the few studies we have on the subject are limited in scope, and some of them are the work of a single team. At this stage of knowledge, it is difficult to conclude on the existence of a bidirectional link between the brain and the oral microbiome. Future studies on the subject will clarify these questions that for the moment remain unresolved.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ashraf Z. Badros ◽  
Mariam Meddeb ◽  
Dianna Weikel ◽  
Sunita Philip ◽  
Todd Milliron ◽  
...  

PurposeDefine incidence and risk factors of osteonecrosis of the jaw (ONJ) and explore oral microbial signatures and host immune response as reflected by cytokine changes in saliva and serum in multiple myeloma (MM) patients on bisphosphate (BP) therapy.Patients and MethodsA single center observational prospective study of MM patients (n = 110) on >2 years of BP, none had ONJ at enrollment. Patients were followed every 3 months for 18 months with clinical/dental examination and serial measurements of inflammatory cytokines, bone turnover markers, and angiogenic growth factors. Oral microbiota was characterized by sequencing of 16S rRNA gene from saliva.ResultsOver the study period 14 patients (13%) developed BRONJ, at a median of 5.7 years (95% CI: 1.9–12.0) from MM diagnosis. Chronic periodontal disease was the main clinically observed risk factor. Oral microbial profiling revealed lower bacterial richness/diversity in BRONJ. Streptococcus intermedius, S. mutans, and S. perioris were abundant in controls; S. sonstellatus and S anginosus were prevalent in BRONJ. In the saliva, at baseline patients who developed BRONJ had higher levels of MIP-1β; TNF-α and IL-6 compared to those without BRONJ, cytokine profile consistent with M-1 macrophage activation. In the serum, patients with BRONJ have significantly lower levels of TGF beta and VEGF over the study period.ConclusionPeriodontal disease associated with low microbial diversity and predominance of invasive species with a proinflammatory cytokine profile leading to tissue damage and alteration of immunity seems to be the main culprit in pathogenesis of BRONJ.


2019 ◽  
Vol 51 (12) ◽  
pp. 1-6 ◽  
Author(s):  
Yuichi Maeda ◽  
Kiyoshi Takeda

AbstractThe gut microbiota has been proposed to be an important environmental factor in the development of rheumatoid arthritis (RA). Here, we review a growing body of evidence from human and animal studies that supports the hypothesis that intestinal microbiota play a role in RA. Previous studies from we and others showed an altered composition of the microbiota in early RA patients. A recent study demonstrated that Prevotella species are dominant in the intestine of patients in the preclinical stages of RA. In addition, Prevotella-dominated microbiota isolated from RA patients contributes to the development of Th17 cell-dependent arthritis in SKG mice. Moreover, it was reported that periodontal bacteria correlates with the pathogenesis of RA. In this review, we discuss the link between oral bacteria and the development of arthritis. However, many questions remain to be elucidated in terms of molecular mechanisms for the involvement of intestinal and oral microbiota in RA pathogenesis.


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