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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2020

01-12-2020 | Arthritis | Research article

Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model

Authors: Yuta Hamamoto, Kazuhisa Ouhara, Syuichi Munenaga, Mikio Shoji, Tatsuhiko Ozawa, Jyunzo Hisatsune, Isamu Kado, Mikihito Kajiya, Shinji Matsuda, Toshihisa Kawai, Noriyoshi Mizuno, Tsuyoshi Fujita, Shintaro Hirata, Kotaro Tanimoto, Koji Nakayama, Hiroyuki Kishi, Eiji Sugiyama, Hidemi Kurihara

Published in: Arthritis Research & Therapy | Issue 1/2020

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Abstract

Background

Porphyromonas gingivalis (Pg) infection causes periodontal disease and exacerbates rheumatoid arthritis (RA). It is reported that inoculation of periodontopathogenic bacteria (i.e., Pg) can alter gut microbiota composition in the animal models. Gut microbiota dysbiosis in human has shown strong associations with systemic diseases, including RA, diabetes mellitus, and inflammatory bowel disease. Therefore, this study investigated dysbiosis-mediated arthritis by Pg oral inoculation in an experimental arthritis model mouse.

Methods

Pg inoculation in the oral cavity twice a week for 6 weeks was performed to induce periodontitis in SKG mice. Concomitantly, a single intraperitoneal (i.p.) injection of laminarin (LA) was administered to induce experimental arthritis (Pg-LA mouse). Citrullinated protein (CP) and IL-6 levels in serum as well as periodontal, intestinal, and joint tissues were measured by ELISA. Gut microbiota composition was determined by pyrosequencing the 16 s ribosomal RNA genes after DNA purification of mouse feces. Fecal microbiota transplantation (FMT) was performed by transferring Pg-LA-derived feces to normal SKG mice. The effects of Pg peptidylarginine deiminase (PgPAD) on the level of citrullinated proteins and arthritis progression were determined using a PgPAD knockout mutant.

Results

Periodontal alveolar bone loss and IL-6 in gingival tissue were induced by Pg oral infection, as well as severe joint destruction, increased arthritis scores (AS), and both IL-6 and CP productions in serum, joint, and intestinal tissues. Distribution of Deferribacteres and S24-7 was decreased, while CP was significantly increased in gingiva, joint, and intestinal tissues of Pg-inoculated experimental arthritis mice compared to experimental arthritis mice without Pg inoculation. Further, FMT from Pg-inoculated experimental arthritis mice reproduced donor gut microbiota and resulted in severe joint destruction with increased IL-6 and CP production in joint and intestinal tissues. The average AS of FMT from Pg-inoculated experimental arthritis was much higher than that of donor mouse. However, inoculation of the PgPAD knockout mutant inhibited the elevation of arthritis scores and ACPA level in serum and reduced CP amount in gingival, joint, and intestinal tissues compared to Pg wild-type inoculation.

Conclusion

Pg oral infection affected gut microbiota dysbiosis and joint destruction via increased CP generation.
Appendix
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Metadata
Title
Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model
Authors
Yuta Hamamoto
Kazuhisa Ouhara
Syuichi Munenaga
Mikio Shoji
Tatsuhiko Ozawa
Jyunzo Hisatsune
Isamu Kado
Mikihito Kajiya
Shinji Matsuda
Toshihisa Kawai
Noriyoshi Mizuno
Tsuyoshi Fujita
Shintaro Hirata
Kotaro Tanimoto
Koji Nakayama
Hiroyuki Kishi
Eiji Sugiyama
Hidemi Kurihara
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2020
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-020-02348-z

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