Differences in the Oral Microbiome in Patients With Early Rheumatoid Arthritis and Individuals at Risk of Rheumatoid Arthritis Compared to Healthy Individuals

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/12

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

33949151

DOI Digital object identifier for electronic documents.

10.1002/art.41780

URI

Authors

Kroese JM, Brandt BW, Buijs MJ, Crielaard W, Lobbezoo F, Loos BG, van Boheemen L, van Schaardenburg D, Zaura E, Volgenant CMC

Journal

Arthritis & rheumatology (Hoboken, N.J.)

Year

2021

OBJECTIVE: It has been suggested that rheumatoid arthritis (RA) may originate at the oral mucosa. The aim of the present study was to assess the oral microbiome and periodontal condition in patients with early RA and individuals at risk of developing RA compared to healthy controls. METHODS: Three groups were recruited (n = 50 participants per group): 1) patients with early RA (meeting the American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 classification criteria), 2) individuals at risk of developing RA (those with arthralgia who were positive for RA-associated autoantibodies), and 3) healthy controls. A periodontal examination was conducted to assess the presence of bleeding on probing (BOP), pocket probing depth (PPD), and periodontal inflamed surface area (PISA). The microbial composition of subgingival dental plaque, saliva, and tongue coating was assessed using 16S ribosomal DNA amplicon sequencing, and findings were compared between groups with permutational multivariate analysis of variance (PERMANOVA). RESULTS: There were no significant differences in any of the 3 periodontal variables between patients with early RA, at-risk individuals, and healthy controls (P = 0.70 for BOP, P = 0.30 for PPD, and P = 0.57 for PISA, by Kruskal-Wallis test). PERMANOVA analyses comparing microbial composition between the groups showed significant differences in the microbial composition of saliva (F = 2.08, P = 0.0002) and tongue coating (F = 2.04, P = 0.008), but not subgingival dental plaque (F = 0.948, P = 0.51). However, in post hoc tests, no significant differences in microbial composition of the saliva or tongue coating were observed between the early RA group and the at-risk group (F = 1.12, P = 0.28 for saliva; F = 0.834, P = 0.59 for tongue coating). In assessing microbial diversity based on the number of zero-radius operational taxonomic units per sample, Prevotella in the saliva and Veillonella in the saliva and tongue coating were each found at a higher relative abundance in samples from patients with early RA and at-risk individuals compared to healthy controls. CONCLUSION: The results show similarities in the oral microbiome between patients with early RA and at-risk individuals, since in both groups, the oral microbiome was characterized by an increased relative abundance of potentially proinflammatory species when compared to that in healthy controls. These findings suggest a possible association between the oral microbiome and the onset of RA.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/12

Curated date: 2022/11/09

Curator: Tislam

Revision editor(s): WikiWorks, Claregrieve1, Tislam, Peace Sandy

Subjects

Location of subjects: Netherlands

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Saliva

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Arthritis arthritic joint disease,arthritides,arthritis,inflammation of skeletal joint,inflammatory disorder of joint,skeletal joint inflammation,Arthritis

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy control

Group 1 name Corresponds to the case (exposed) group for case-control studies: Early Rheumatoid Arthritis

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Early Rheumatoid Arthritis patients (diagnosed within the previous year)

Group 0 sample size Number of subjects in the control (unexposed) group: 50

Group 1 sample size Number of subjects in the case (exposed) group: 50

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 3 months

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3

Matched on Factors on which subjects have been matched on in a case-control study: age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Richness Number of species: unchanged

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Source: Supplementary Table 3

Description: Saliva: a summary of the most significant zero-radius operational taxonomic units (zOTUs) that differentiated among the early rheumatoid arthritis (RA) group, at-risk group, and control group, sorted on linear discriminant analysis (LDA) score per group. Differences in relative abundance among the groups were tested with a Kruskal-Wallis test (false discovery rate corrected level of significance of 0.02), and post-hoc Mann-Whitney U tests. Results for zOTUs with a median relative abundance ≥0.01 for ≥1 group are marked with an outline.

Abundance in Group 1: decreased abundance in Early Rheumatoid Arthritis

NCBI	Quality Control	Links
Porphyromonas pasteri
Fusobacterium periodonticum
Veillonella parvula
Veillonella
Hoylesella nanceiensis
Alloprevotella
Granulicatella
Neisseria flavescens
Neisseria subflava
Streptococcus oralis subsp. dentisani
Streptococcus oralis
Streptococcus infantis
Streptococcus mitis

Revision editor(s): Tislam, Atrayees, WikiWorks

Signature 2

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Mark reviewed

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Needs review

Curated date: 2022/11/09

Curator: Tislam

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Source: Supplementary Table 3

Description: Saliva: a summary of the most significant zero-radius operational taxonomic units (zOTUs) that differentiated among the early rheumatoid arthritis (RA) group, at-risk group, and control group, sorted on linear discriminant analysis (LDA) score per group. Differences in relative abundance among the groups were tested with a Kruskal-Wallis test (false discovery rate corrected level of significance of 0.02), and post-hoc Mann-Whitney U tests. Results for zOTUs with a median relative abundance ≥0.01 for ≥1 group are marked with an outline.

Abundance in Group 1: increased abundance in Early Rheumatoid Arthritis

NCBI	Quality Control	Links
Streptococcus salivarius
Streptococcus vestibularis
Streptococcus sanguinis
Segatella salivae
Streptococcus
Rothia mucilaginosa
Selenomonas
Streptococcus downei
Streptococcus sobrinus

Revision editor(s): Tislam, Atrayees, WikiWorks