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

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/12
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


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 Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,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

Signature 1

Reviewed Marked as Reviewed by Atrayees on 2023-7-20

Curated date: 2022/11/09

Curator: Tislam

Revision editor(s): Tislam, Atrayees

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 ControlLinks
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

Signature 2

Reviewed Marked as Reviewed by Atrayees on 2023-7-20

Curated date: 2022/11/09

Curator: Tislam

Revision editor(s): Tislam, Atrayees

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 ControlLinks
Streptococcus salivarius
Streptococcus vestibularis
Streptococcus sanguinis
Segatella salivae
Streptococcus
Rothia mucilaginosa
Selenomonas
Streptococcus downei
Streptococcus sobrinus

Revision editor(s): Tislam, Atrayees