Identification of human-derived gut microbes involved in the inflammation in the central nerve system

• Project/Area Number: 16K18711
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Food science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Miyauchi Eiji 国立研究開発法人理化学研究所, 生命医科学研究センター, 基礎科学特別研究員 (60634706)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 多発性硬化症 / 腸内細菌 / 自己免疫疾患 / 脳神経疾患 / 食品

Outline of Final Research Achievements

It has been reported that gut microbiota affects the development of mutiple sclerosis, MS. Studies using a mouse model demonstrated that some microbes colonized in mice, such as filamentous bacteria bacteria (SFB), increase proinflammatory responses both in the intestine and central nerve system. In this study, we identified human-derived microbes which play a role in the inflammation in the spinal cords. In addition, we demonstrated that dietary ingredients, such as fibers, are able to modulate gut microbiota, and this leads to suppressive effects on the inflammation in the spinal cords.

Academic Significance and Societal Importance of the Research Achievements

近年、多発性硬化症患者の腸内細菌叢は健常人とは異なるという報告が多くなされている。このことは、ある種の腸内細菌が中枢神経系に炎症に加担していることを示唆するとともに、腸内細菌叢を制御することで、多発性硬化症などの炎症疾患を抑制することを示唆している。本研究では中枢神経系炎症に関与するヒト腸内細菌細菌を食事内容により制御できることを示した。今後、多発性硬化症患者に対し食事内容を整えることが治療に繋がるか、検討が望まれる。

Research Products

• [Journal Article] Intestinal IgA as a modulator of the gut microbiota. (2017)
  • Author(s): Okai S, Usui F, Ohta M, Mori H, Kurokawa K, Matsumoto S, Kato T, Miyauchi E, Ohno H, Shinkura R.
  • Journal Title: Gut Microbes Volume: - Issue: 5 Pages: 1-7
  • DOI: 10.1080/19490976.2017.1310357
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice. (2016)
  • Author(s): Okai S, Usui F, Yokota S, Hori-I Y, Hasegawa M, Nakamura T, Kurosawa M, Okada S, Yamamoto K, Nishiyama E, Mori H, Yamada T, Kurokawa K, Matsumoto S, Nanno M, Naito T, Watanabe Y, Kato T, Miyauchi E, Ohno H, Shinkura R.
  • Journal Title: Nature Microbiology Volume: 1 Issue: 9 Pages: 16103-16103
  • DOI: 10.1038/nmicrobiol.2016.103
  • NAID: 120005818448
  • Peer Reviewed / Open Access
• [Journal Article] 腸内細菌と腸管免疫の相互作用 (2016)
  • Author(s): 宮内栄治、大野博司
  • Journal Title: 月刊カレントテラピー Volume: 34 Pages: 13-18
• [Presentation] The effects of smoking on gut ecosystem of patients with IBD (2018)
  • Author(s): Miyauchi E., Nakanishi K., Uchiyama K., Koido S., Arakawa H., Kawasumi M., Ito A., Ohkusa T. and Ohno H
  • Organizer: FALK Symposium 212
  • Int'l Joint Research
• [Presentation] Small intestinal microbes act in concert to exacerbate autoimmune inflammation in the central nervous system (2018)
  • Author(s): Miyauchi E. and Ohno H.
  • Organizer: IMS-JSI International Symposium on Immunology 2018 "Checkpoint in medical science and its technology"
  • Int'l Joint Research
• [Presentation] Gut microbial metabolite acetate promotes bacteria-specific IgA production to maintain intestinal homeostasis (2018)
  • Author(s): Takeuchi T., Miyauchi E., and Ohno H.
  • Organizer: 2nd Korea-Japan Joint Meeting on Mucosal Immunology
  • Int'l Joint Research
• [Presentation] Gut microbial metabolite acetate tunes IgA reactivity toward commensal microbes to maintain mucosal homeostasis (2018)
  • Author(s): Takeuchi T., Miyauchi E., Shimamoto S., Matsuyama A., and Ohno H.
  • Organizer: The 47th Annual Meeting of the Japanese Society for Immunology
• [Presentation] Microbiota-dependent and -independent induction of colonic regulatory T cells by butyrate (2018)
  • Author(s): Negishi H., Takeuchi T., Miyauchi E., Shimamoto S., Matsuyama A., and Ohno H.
  • Organizer: The 47th Annual Meeting of the Japanese Society for Immunology
• [Presentation] The Role of Gut Microbiota in the Pathogenesis of Experimental Autoimmune Encephalomyelitis (2017)
  • Author(s): Eiji Miyauchi, Seok-Won Kim, Wataru Suda, Masahira Hattori, Todd D. Taylor, Hiroshi Ohno
  • Organizer: 18th International Congress of Mucosal Immunology
  • Int'l Joint Research
• [Presentation] Mimicry peptides from gut commensals stimulate myelin-specific T cells and exacerbate experimental autoimmune encephalomyelitis (2017)
  • Author(s): Eiji Miyauchi, Seok-Won Kim, Hiroshi Ohno
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] The effects of smoking on gut ecosystem in IBD (2017)
  • Author(s): Eiji Miyauchi, Yumiko Sato, Kan Yamauchi, Shigeo Koido, Hiroshi Arakawa, Masami Kawasumi, Ayumi Ito, Toshifumi Ohkusa, Hiroshi Ohno
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 多発性硬化症モデルマウスにおける腸内細菌の役割 (2016)
  • Author(s): 宮内栄治、大野博司
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
  • Invited
• [Book] 実験医学増刊号 腸内細菌叢 : 健康と疾患を制御するエコシステム（多発性硬化症における腸内細菌の影響） (2019)
  • Author(s): 宮内栄治、大野博司
  • Total Pages: 4
  • Publisher: 羊土社
  • ISBN: 9784758103763
• [Book] Precision Medicine 腸管フローラと個別化医療（腸内細菌叢と腸管免疫） (2019)
  • Author(s): 宮内栄治、大野博司
  • Total Pages: 4
  • Publisher: 北隆館
• [Book] 化学工業 (2018)
  • Author(s): 宮内栄治、大野博司
  • Total Pages: 8
  • Publisher: 化学工業社