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. 2022 Aug 31;23(17):9883.
doi: 10.3390/ijms23179883.

Subgingival Microbiome in Rheumatoid Arthritis Patients with Periodontitis

Yi-Jing Chen  1 , Wei-Chun Hung  1 , Yu-Hsiang Chou  2   3 , Chern-Hsiung Lai  3   4 , Po Peng  5 , Pei-Syuan Jhou  1 , Min-Ru Tsai  1 , Jim Jinn-Chyuan Sheu  6   7 , Jeng-Hsien Yen  8   9
Affiliations

Subgingival Microbiome in Rheumatoid Arthritis Patients with Periodontitis

Yi-Jing Chen et al. Int J Mol Sci. .

Abstract

Rheumatoid arthritis (RA) and periodontitis are suggested to be closely linked based on microbial dysbiosis, but limited subgingival bacteria have been proven in the pathogenesis of RA. We enrolled 30 RA patients and 25 controls and divided them into three groups with matched age, gender, and diabetes statuses: group AM (all of the matched participants), group PD (periodontally diseased), and group PH (periodontally healthy). Their subgingival microbial composition was determined by V3-V4 16S rRNA gene sequencing. Significant differences in subgingival microbial clustering between the RA patients and controls were observed in groups AM and PD. Among the taxa enriched in RA, Aminipila butyrica and Peptococcus simiae were the only two species displaying positive correlation to the level of anti-citrullinated protein antibodies (ACPAs) in both of the groups. Surprisingly, the median of relative abundances of A. butyrica and P. simiae were 0% in the controls of group PD. Furthermore, a gene encoding arginine deiminase with the capability to produce citrulline was addressed in the complete genome sequence of A. butyrica. This is the first study to elucidate the important roles of A. butyrica and P. simiae as periodontal bacteria leading to RA possibly through the induction of ACPA production.

Keywords: anti-citrullinated protein antibody (ACPA); microbial dysbiosis; periodontitis; rheumatoid arthritis; subgingival microbiome.

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Conflict of interest statement

The authors declare that there is no conflict of interest in this study.

Figures

Figure 1
Figure 1
Study design and the flowchart. A total of 42, 24, and 12 participants were eligible for the final analysis in groups AM, PD, and PH, respectively. The RA and control participants were matched on age, gender, and DM statuses.
Figure 2
Figure 2
The intra-group diversity of subgingival microbiota in groups AM, PD, and PH. (A) The number of the observed bacterial features, (B) Chao1 index, and (C) Shannon index. The RA patients are indicated in orange, and the controls are indicated in blue. The data are expressed as median (25th, 75th percentile). *, p < 0.05.
Figure 3
Figure 3
The subgingival microbiota clustering by PCoA based on Bray–Curtis dissimilarity between the RA patients (orange dots) and controls (blue triangles). (A) Group AM (ANOSIM: R = 0.177, p = 0.001 and PERMANOVA: pseudo-F = 2.561, p = 0.001), (B) group PD (ANOSIM: R = 0.15, p = 0.013 and PERMANOVA: pseudo-F = 1.722, p = 0.018), and (C) group PH (ANOSIM: R = 0.167, p = 0.116 and PERMANOVA: pseudo-F = 1.449, p = 0.076).
Figure 4
Figure 4
Relative abundances of (A) A. butyrica and (B) P. simiae displaying positive correlations to the ACPA levels in both of groups AM and PD. RA, the RA patients in this study; Control, the controls in this study. The data are expressed as median (25th, 75th percentile).
See this image and copyright information in PMC

References

    1. Lundberg K., Wegner N., Yucel-Lindberg T., Venables P.J. Periodontitis in RA—The citrullinated enolase connection. Nat. Rev. Rheumatol. 2010;6:727–730. doi: 10.1038/nrrheum.2010.139. - DOI - PubMed
    1. Alghamdi M.A., Redwan E.M. Interplay of Microbiota and Citrullination in the Immunopathogenesis of Rheumatoid Arthritis. Probiotics Antimicrob. Proteins. 2021;14:99–113. doi: 10.1007/s12602-021-09802-7. - DOI - PubMed
    1. Zhou Y., Chen B., Mittereder N., Chaerkady R., Strain M., An L.-L., Rahman S., Ma W., Low C.P., Chan D., et al. Spontaneous Secretion of the Citrullination Enzyme PAD2 and Cell Surface Exposure of PAD4 by Neutrophils. Front. Immunol. 2017;8:1200. doi: 10.3389/fimmu.2017.01200. - DOI - PMC - PubMed
    1. Kroot E.-J.J.A., De Jong B.A.W., Van Leeuwen M.A., Swinkels H., Hoogen F.H.J.V.D., Hof M.V., Van De Putte L.B.A., Van Rijswijk M.H., Van Venrooij W.J., Van Riel P.L.C.M. The prognostic value of anti-cyclic citrullinated peptide antibody in patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 2000;43:1831–1835. doi: 10.1002/1529-0131(200008)43:8<1831::AID-ANR19>3.0.CO;2-6. - DOI - PubMed
    1. Mankia K., Cheng Z., Do T., Hunt L., Meade J., Kang J., Clerehugh V., Speirs A., Tugnait A., Hensor E.M.A., et al. Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti–Cyclic Citrullinated Protein Antibody–Positive At-Risk Adults without Arthritis. JAMA Netw. Open. 2019;2:e195394. doi: 10.1001/jamanetworkopen.2019.5394. - DOI - PMC - PubMed

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