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Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574451/ https://www.ncbi.nlm.nih.gov/pubmed/33076980 http://dx.doi.org/10.1186/s13075-020-02348-z |
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author | Hamamoto, Yuta Ouhara, Kazuhisa Munenaga, Syuichi Shoji, Mikio Ozawa, Tatsuhiko Hisatsune, Jyunzo Kado, Isamu Kajiya, Mikihito Matsuda, Shinji Kawai, Toshihisa Mizuno, Noriyoshi Fujita, Tsuyoshi Hirata, Shintaro Tanimoto, Kotaro Nakayama, Koji Kishi, Hiroyuki Sugiyama, Eiji Kurihara, Hidemi |
author_facet | Hamamoto, Yuta Ouhara, Kazuhisa Munenaga, Syuichi Shoji, Mikio Ozawa, Tatsuhiko Hisatsune, Jyunzo Kado, Isamu Kajiya, Mikihito Matsuda, Shinji Kawai, Toshihisa Mizuno, Noriyoshi Fujita, Tsuyoshi Hirata, Shintaro Tanimoto, Kotaro Nakayama, Koji Kishi, Hiroyuki Sugiyama, Eiji Kurihara, Hidemi |
author_sort | Hamamoto, Yuta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7574451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75744512020-10-20 Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model Hamamoto, Yuta Ouhara, Kazuhisa Munenaga, Syuichi Shoji, Mikio Ozawa, Tatsuhiko Hisatsune, Jyunzo Kado, Isamu Kajiya, Mikihito Matsuda, Shinji Kawai, Toshihisa Mizuno, Noriyoshi Fujita, Tsuyoshi Hirata, Shintaro Tanimoto, Kotaro Nakayama, Koji Kishi, Hiroyuki Sugiyama, Eiji Kurihara, Hidemi Arthritis Res Ther Research Article 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. BioMed Central 2020-10-19 2020 /pmc/articles/PMC7574451/ /pubmed/33076980 http://dx.doi.org/10.1186/s13075-020-02348-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Hamamoto, Yuta Ouhara, Kazuhisa Munenaga, Syuichi Shoji, Mikio Ozawa, Tatsuhiko Hisatsune, Jyunzo Kado, Isamu Kajiya, Mikihito Matsuda, Shinji Kawai, Toshihisa Mizuno, Noriyoshi Fujita, Tsuyoshi Hirata, Shintaro Tanimoto, Kotaro Nakayama, Koji Kishi, Hiroyuki Sugiyama, Eiji Kurihara, Hidemi Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model |
title | Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model |
title_full | Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model |
title_fullStr | Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model |
title_full_unstemmed | Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model |
title_short | Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model |
title_sort | effect of porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574451/ https://www.ncbi.nlm.nih.gov/pubmed/33076980 http://dx.doi.org/10.1186/s13075-020-02348-z |
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