Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

32039051

DOI Digital object identifier for electronic documents.

10.3389/fcimb.2019.00475

URI

Authors

Tong Y, Zheng L, Qing P, Zhao H, Li Y, Su L, Zhang Q, Zhao Y, Luo Y, Liu Y

Journal

Frontiers in cellular and infection microbiology

Year

2019

Keywords:

anti-citrullinated protein autoantibodies, dysbiosis, high risk, oral microbiome, rheumatoid arthritis

Oral microbial dysbiosis is known to increase susceptibility of an individual to develop rheumatoid arthritis (RA). Individuals at-risk of RA may undergo different phases of disease progression. In this study, we aim to investigate whether and whereby the oral microbiome communities alter prior to symptoms of RA. Seventy-nine saliva samples were collected from 29 high-risk individuals, who were positive for anti-citrullinated protein antibodies (ACPA) and have no clinical arthritis, 27 RA patients and 23 healthy controls (HCs). The salivary microbiome was examined using 16S ribosomal RNA gene sequencing. Alpha and beta diversity analysis and the linear discriminant analysis were applied to examine the bacterial diversity, community structure and discriminatory taxa between three groups, respectively. The correlation between salivary bacteria and autoantibodies were analyzed. In the "pre-clinical" stages, salivary microbial diversity was significantly reduced comparing to RA patients and HCs. In contrast to HCs, like RA patients, individuals at high-risk for RA showed a reduction in the abundance of genus Defluviitaleaceae_UCG-011 and the species Neisseria oralis, but an expansion of Prevotella_6. Unexpectedly, the relative abundance of Porphyromonas gingivalis, reported as opportunistic pathogens for RA development, was significantly decreased in high-risk individuals. Additionally, we identified four genera in the saliva from high-risk individuals positively correlated with serum ACPA titers, and the other two genera inversely displayed. In summary, we observed a characteristic compositional change of salivary microbes in individuals at high-risk for RA, suggesting that oral microbiota dysbiosis occurs in the "pre-clinical" stage of RA and are correlated with systemic autoimmune features.

Experiment 1

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Curated date: 2021/08/16

Curator: Tislam

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Subjects

Location of subjects: China

Host species Species from which microbiome was sampled (if applicable): 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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: rheumatoid arthritis Arthritis or polyarthritis, rheumatic,arthritis or polyarthritis, rheumatic,Arthritis, Rheumatoid,arthritis, rheumatoid,atrophic Arthritis,atrophic arthritis,autoimmune arthritis,Chronic rheumatic arthritis,Proliferative arthritis,RA,RA - Rheumatoid arthritis,RhA - Rheumatoid arthritis,Rheumatic gout,rheumatoid arthritis,Rheumatoid arthritis (disorder),Rheumatoid arthritis NOS,Rheumatoid arthritis NOS (disorder),rheumatoid arthritis, susceptibility to,Rheumatoid disease

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies: rheumatoid arthritis patient
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: rheumatoid arthritis patient
Group 0 sample size Number of subjects in the control (unexposed) group: 23
Group 1 sample size Number of subjects in the case (exposed) group: 27
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Individuals having a history of antibiotics treatment or surgery in the last 3 months were excluded

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

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

Statistical Analysis

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): .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, ethnic group, sex

Alpha Diversity

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

Signature 1

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Curated date: 2021/08/16

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Source: Figure 3B, text

Description: Figure 3. LEfSe analysis revealed the specific taxa changes in high-risk individuals (Pre) and RA patients. LefSe analysis was applied to identify differentially abundant taxa, which are highlighted on the phylogenetic tree in cladogram format (A) and for which the LDA scores more than 3 are shown (B).

Abundance in Group 1: increased abundance in rheumatoid arthritis patient

NCBI	Quality Control	Links
Actinomyces
Actinomyces graevenitzii
Actinomycetales
Actinomycetota
Atopobiaceae
Atopobium
Bacillales
Bacillota
Candidatus Saccharimonadales
Candidatus Saccharimonadia
Coriobacteriales
Gemella
Megasphaera
Negativicutes
Patescibacteria group
Prevotella
Selenomonadales
Selenomonas
Veillonellaceae
Treponema

Revision editor(s): Tislam, Atrayees

Signature 2

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Curated date: 2021/08/17

Curator: Tislam

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Source: Figure 3, text

Description: LEfSe analysis revealed the specific taxa changes in high-risk individuals (Pre) and RA patients. LefSe analysis was applied to identify differentially abundant taxa, which are highlighted on the phylogenetic tree in cladogram format

Abundance in Group 1: decreased abundance in rheumatoid arthritis patient

NCBI	Quality Control	Links
Betaproteobacteria
Filifactor
Haemophilus
Neisseria
Pasteurellaceae
Pasteurellales
Porphyromonadaceae
Porphyromonas
Spirochaeta
Spirochaetaceae
Spirochaetales
Spirochaetota

Revision editor(s): Tislam