Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis

From BugSigDB
Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2021/08/16

Curator: Tislam

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

Subjects

Location of subjects
China
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
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,Rheumatoid arthritis
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
Pre - High risk Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Pre, “pre-clinical” at risk for RA individuals; RF, rheumatoid factor; ACPA, anti-citrullinated protein antibodies;
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
29
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

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, ethnic group, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
decreased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
decreased

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2021/08/16

Curator: Tislam

Revision editor(s): Tislam, Atrayees, Peace Sandy

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 and for which the LDA scores more than 3 are shown (B). LefSe, the LDA effect size. *p < 0.05; **p < 0.01; and ***p < 0.001.

Abundance in Group 1: increased abundance in Pre - High risk Patients

NCBI Quality ControlLinks
Bacillales
Gemella

Revision editor(s): Tislam, Atrayees, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2021/08/17

Curator: Tislam

Revision editor(s): Tislam, Peace Sandy

Source: Figure 3, 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 and for which the LDA scores more than 3 are shown (B). LefSe, the LDA effect size. *p < 0.05; **p < 0.01; and ***p < 0.001.

Abundance in Group 1: decreased abundance in Pre - High risk Patients

NCBI Quality ControlLinks
Filifactor
Gammaproteobacteria
Haemophilus
Neisseria
Neisseriaceae
Pasteurellaceae
Pasteurellales
Porphyromonadaceae
Porphyromonas
Pseudomonadales
Pseudomonadota
Spirochaeta
Spirochaetaceae
Spirochaetales
Spirochaetia

Revision editor(s): Tislam, Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2024/01/21

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

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,Rheumatoid arthritis
Group 1 name Corresponds to the case (exposed) group for case-control studies
Rheumatoid Arthritis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Rheumatoid Arthritis
Group 1 sample size Number of subjects in the case (exposed) group
27

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
decreased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
decreased

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2024/01/21

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3, 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 and for which the LDA scores more than 3 are shown (B). LefSe, the LDA effect size. *p < 0.05; **p < 0.01; and ***p < 0.001.

Abundance in Group 1: increased abundance in Rheumatoid Arthritis

NCBI Quality ControlLinks
Bacillota
Negativicutes
Selenomonadales
Veillonellaceae
Actinomycetota
Actinomycetales
Actinomycetaceae
Actinomyces
Candidatus Saccharimonadales
Treponema
Selenomonas
Prevotella
Megasphaera
Coriobacteriales
Atopobiaceae
Atopobium

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2024/01/21

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3, 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 and for which the LDA scores more than 3 are shown (B). LefSe, the LDA effect size. *p < 0.05; **p < 0.01; and ***p < 0.001.

Abundance in Group 1: decreased abundance in Rheumatoid Arthritis

NCBI Quality ControlLinks
Filifactor
Gammaproteobacteria
Haemophilus
Neisseria
Neisseriaceae
Pasteurellaceae
Pasteurellales
Porphyromonadaceae
Porphyromonas
Pseudomonadales
Pseudomonadota
Spirochaetaceae
Spirochaetales
Spirochaetia
Spirochaeta

Revision editor(s): Peace Sandy

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2024/01/21

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Rheumatoid Arthritis
Group 1 name Corresponds to the case (exposed) group for case-control studies
Pre - High risk Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Pre, “pre-clinical” at risk for RA individuals; RF, rheumatoid factor; ACPA, anti-citrullinated protein antibodies;
Group 0 sample size Number of subjects in the control (unexposed) group
27
Group 1 sample size Number of subjects in the case (exposed) group
29

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Richness Number of species
decreased
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
decreased

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2024/01/21

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3, 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 and for which the LDA scores more than 3 are shown (B). LefSe, the LDA effect size. *p < 0.05; **p < 0.01; and ***p < 0.001.

Abundance in Group 1: increased abundance in Pre - High risk Patients

NCBI Quality ControlLinks
Bacillales
Gemella

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-21

Curated date: 2024/01/21

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Figure 3, 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 and for which the LDA scores more than 3 are shown (B). LefSe, the LDA effect size. *p < 0.05; **p < 0.01; and ***p < 0.001.

Abundance in Group 1: decreased abundance in Pre - High risk Patients

NCBI Quality ControlLinks
Actinomyces
Actinomycetaceae
Actinomycetales
Actinomycetota
Atopobiaceae
Bacillota
Candidatus Saccharimonadales
Coriobacteriales
Megasphaera
Negativicutes
Patescibacteria group
Prevotella
Selenomonadales
Selenomonas
Treponema
Veillonellaceae
Atopobium

Revision editor(s): Peace Sandy