The subgingival microbiome in patients with established rheumatoid arthritis

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

29562298

DOI Digital object identifier for electronic documents.

10.1093/rheumatology/key052

URI Uniform resource identifier for web resources.

Authors

Mikuls TR, Walker C, Qiu F, Yu F, Thiele GM, Alfant B, Li EC, Zhao LY, Wang GP, Datta S, Payne JB

Journal

Rheumatology (Oxford, England)

Year

2018

OBJECTIVES: To profile and compare the subgingival microbiome of RA patients with OA controls. METHODS: RA (n = 260) and OA (n = 296) patients underwent full-mouth examination and subgingival samples were collected. Bacterial DNA was profiled using 16 S rRNA Illumina sequencing. Following data filtering and normalization, hierarchical clustering analysis was used to group samples. Multivariable regression was used to examine associations of patient factors with membership in the two largest clusters. Differential abundance between RA and OA was examined using voom method and linear modelling with empirical Bayes moderation (Linear Models for Microarray Analysis, limma), accounting for the effects of periodontitis, race, marital status and smoking. RESULTS: Alpha diversity indices were similar in RA and OA after accounting for periodontitis. After filtering, 286 taxa were available for analysis. Samples grouped into one of seven clusters with membership sizes of 324, 223, 3, 2, 2, 1 and 1 patients, respectively. RA-OA status was not associated with cluster membership. Factors associated with cluster 1 (vs 2) membership included periodontitis, smoking, marital status and Caucasian race. Accounting for periodontitis, 10 taxa (3.5% of those examined) were in lower abundance in RA than OA. There were no associations between lower abundance taxa or other select taxa examined with RA autoantibody concentrations. CONCLUSION: Leveraging data from a large case-control study and accounting for multiple factors known to influence oral health status, results from this study failed to identify a subgingival microbial fingerprint that could reliably discriminate RA from OA patients.

Experiment 1

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Curated date: 2022/11/02

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Subjects

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: Subgingival dental plaque Subgingival plaque,Subgingival dental plaque

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

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Osteoarthritis with periodontitis
Group 1 name Corresponds to the case (exposed) group for case-control studies: Rheumatoid Arthritis with periodontitis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Rheumatoid Arthritis patients with periodontitis
Group 0 sample size Number of subjects in the control (unexposed) group: 81
Group 1 sample size Number of subjects in the case (exposed) group: 99

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V3

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

Statistical Analysis

Statistical test: Linear Regression

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: comorbidity, marital status, race, smoking status

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged
Chao1 Abundance-based estimator of species richness: unchanged
Richness Number of species: unchanged

Signature 1

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Description: Excluding taxa for which >75% of patients in all four groups had zero values, there were 286 OTUs available for analysis. Among those with periodontitis, there were 10 OTUs (3.5% of OTUs examined) in lower abundance in RA vs OA samples in the base model with false discovery rate-adjusted P-values. These taxa included Catonella sp. (OTU 451), Clostridiales sp. (OTU 85), Lachnospiraceae sp. (OTU 96), Peptostreptococcaceae sp. (OTU 495), Porphyromonas sp. (OTU 285), Prevotella multiformis (OTU 685), Prevotella sp. (OTU 443), Selenomaonas sp. (OTU 479) and Treponema sp. (OTUs 230 and 236) (Table 4). Results were unchanged following full adjustment, with the exception that differential expression of Selenomaonas sp. was no longer significant. Although we observed evidence to suggest the under-abundance of Porphyromonas sp. in RA patients with periodontitis compared with OA patients with periodontitis, there was not similar evidence of differential expression for P. gingivalis (data not shown). In subjects without evidence of periodontitis, only one OTU was found in lower abundance in RA samples and in the fully adjusted model after accounting for false discovery rate, Streptococcus sp. (OTU 486), a difference that did not achieve statistical significance in the base model. There were no OTUs identified in the filtered data consistent with A. actinomycetemcomitans.

Abundance in Group 1: decreased abundance in Rheumatoid Arthritis with periodontitis

NCBI	Links
Catonella
Clostridiales bacterium
Lachnospiraceae
Peptostreptococcaceae
Porphyromonas
Prevotella sp.
Selenomonas
Treponema sp.
Prevotella multiformis

Revision editor(s): Tislam