Understanding the mechanism of action by which the intestinal microbiota affect the pathogenesis of malaria

• Project/Area Number: 16K20952
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology); Epidemiology and preventive medicine
• Research Institution: Gunma University
• Principal Investigator: Taniguchi Tomoyo 群馬大学, 大学院医学系研究科, 助教 (20620800)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: マラリア / 腸内細菌叢 / 腸内細菌 / 脳マラリア / ネズミマラリア / Plasmodium berghei ANKA / dysbiosis / 感染症 / 免疫学 / 寄生虫

Outline of Final Research Achievements

The involvement of the intestinal microbiota in malaria has been reported in recent years. However, the details of how intestinal microbiota affect the pathogenesis of malarial infection remain unknown. In this study, we identified the conditions under which 70% - 80% of mice survived cerebral malaria. The intestinal microbiota of the mice had been markedly changed by the administration of drinking water containing antibiotics. We attempted to elucidate the mechanism of action of the intestinal microbiota under these conditions, and clarified the modulation of the immune response in the small intestine and spleen at the onset of cerebral symptoms. There is a possibility that the intestinal microbiota suppress the migration and accumulation of lymphocytes from organs such as the spleen to the peripheral blood and the brain, resulting in mild brain symptoms.

Academic Significance and Societal Importance of the Research Achievements

本研究により、改めて腸内細菌がマラリア感染病態の軽減・増悪に関わることを示し、腸内細菌を含む新規宿主-マラリア原虫相互作用の存在を明らかにするとともに、その作用機序に免疫応答の変調があることを示した。より詳細な作用機序が明らかになれば、消化器症状の軽減・防御免疫の解明、腸内細菌叢の正常化を主眼とした新たな治療法の開発など、マラリアコントロールの新たな戦略を提案でき、マラリア制圧に向けた予防・治療への可能性が広がる。

Research Products

• [Int'l Joint Research] Gulu University/St. Mary's Hospital Lacor(ウガンダ)
• [Int'l Joint Research] グル大学(ウガンダ)
• [Int'l Joint Research] Faculty of Medicine, Gulu University(ウガンダ)
• [Int'l Joint Research] Center for Malariology, Parasitology(ラオス)
• [Int'l Joint Research] グル大学/St. Mary’s Hospital Lacor, Gulu(ウガンダ)
• [Journal Article] The role of autonomously secreted PGE2 and its autocrine/paracrine effect on bone matrix mineralization at the different stages of differentiating MC3T3-E1 cells (2020)
  • Author(s): Suzuki Hiraku、Ohshima Noriyasu、Tatei Kazuaki、Taniguchi Tomoyo、Sato Seiichi、Izumi Takashi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 524 Issue: 4 Pages: 929-935
  • DOI: 10.1016/j.bbrc.2020.01.120
  • Peer Reviewed / Open Access
• [Journal Article] Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii. (2019)
  • Author(s): Imai T, Suzue K, Ngo-Thanh H, et al.
  • Journal Title: Front Immunol. Volume: 10:2207.
  • DOI: 10.3389/fimmu.2019.02207
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 世界見聞録「感染症と共に生きること」 (2018)
  • Author(s): 谷口委代
  • Journal Title: 月刊新医療 Volume: 7月号 Pages: 26-26
• [Journal Article] マラリア感染に伴う消化器症状と腸内細菌 (2018)
  • Author(s): 谷口委代
  • Journal Title: 臨床免疫・アレルギー科 Volume: 69 Pages: 107-113
  • NAID: 40021436782
  • Peer Reviewed
• [Journal Article] A Unique Subset of γδ T Cells Expands and Produces IL-10 in Patients with Naturally Acquired Immunity against Falciparum Malaria (2017)
  • Author(s): Taniguchi T, Md Mannoor K, Nonaka D, Toma H, Li C, Narita M, Vanisaveth V, Kano S, Takahashi M, Watanabe H
  • Journal Title: Front Microbiol Volume: 8 Pages: 1288-1288
  • DOI: 10.3389/fmicb.2017.01288
  • NAID: 120006845621
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A possible origin population of pathogenic intestinal nematodes, Strongyloides stercoralis, unveiled by molecular phylogeny (2017)
  • Author(s): Nagayasu E, Aung MPPTHH, Hortiwakul T, Hino A, Tanaka T, Higashiarakawa M, Olia A, Taniguchi T, Win SMT, Ohashi I, Odongo-Aginya EI, Aye KM, Mon M, Win KK, Ota K, Torisu Y, Panthuwong S, Kimura E, Palacpac NMQ, Kikuchi T, Hirata T, Torisu S, Hisaeda H, Horii T, Fujita J, Htike WW, Maruyama H
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 4844-4844
  • DOI: 10.1038/s41598-017-05049-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Asymptomatic malaria, growth status, and anaemia among children in Lao People's Democratic Republic: a cross-sectional study (2016)
  • Author(s): Takeshi Akiyama, Tiengkham Pongvongsa, Souraxay Phrommala, Tomoyo Taniguchi, Yuba Inamine, Rie Takeuchi, Tadashi Watanabe, Futoshi Nishimoto, Kazuhiko Moji, Shigeyuki Kano, Hisami Watanabe, and Jun Kobayashi
  • Journal Title: Malaria Journal Volume: 15 Issue: 1 Pages: 499-499
  • DOI: 10.1186/s12936-016-1548-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Altered gut microbiota composition in patients with Plasmodium falciparum malaria (2019)
  • Author(s): Eiji Miyauchi, Tomoyo Taniguchi, Alex Olia, Eiji Nagayasu, Katuro Osbert, Kazutomo Suzue, Takashi Imai, Chikako Shimokawa, Risa Onishi, E.I. Odongo-Aginya, Nirianne Palacpac, Haruhiko Maruyama, Eisaku Kimura, Toshihiro Mita, Toshihiro Horii, Hajime Hisaeda, Hiroshi Ohno
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] A Unique Subset of Gamma Delta T Cells Expands and Produces IL-10 in Patients with Naturally Acquired Immunity against Falciparum Malaria (2019)
  • Author(s): 谷口委代
  • Organizer: 第60回日本熱帯医学会大会
  • Invited
• [Presentation] ネズミマラリア原虫感染における病態形成への腸内細菌の関与 (2019)
  • Author(s): 谷口 委代、鈴江 一友、今井 孝、下川 周子、Olia Alex、久枝 一
  • Organizer: 第88回日本寄生虫学会大会
• [Presentation] ネズミマラリア原虫感染における病態形成への腸内細菌の関与 (2019)
  • Author(s): 谷口 委代、鈴江 一友、今井 孝、下川 周子、Olia Alex、Thanhha Ngo、久枝 一
  • Organizer: 第88回日本寄生虫学会大会
• [Presentation] CD8T 細胞は細胞傷害性分子によりマクロファージと協調してマウス赤内期マラリア感染防御に働く (2019)
  • Author(s): 今井 孝、石田 英和、鈴江 一友、谷口 委代、岡田 紘子、下川 周子、久枝 一
  • Organizer: 第88回日本寄生虫学会大会
• [Presentation] Altered gut microbiota composition in Plasmodium falciparum patients in Uganda (2018)
  • Author(s): Taniguchi T, Miyauchi E, Olia A, Nagayasu E, Osbert K, Suzue K, Imai T, Shimokawa C, Onishi R, Odongo-Aginya E.I., Palacpac Niriann, Maruyama H, Kimura E, Mita T, Ohno H, Horii T and Hisaeda H
  • Organizer: International Congress of Parasitology 2018
  • Int'l Joint Research
• [Presentation] ネズミマラリア原虫感染における免疫応答への腸内細菌の影響 (2018)
  • Author(s): 谷口 委代、鈴江 一友、今井 孝、下川 周子、Olia Alex、久枝 一
  • Organizer: 第87回日本寄生虫学会大会
• [Presentation] ネズミマラリア原虫感染における免疫応答への腸内細菌の影響 (2018)
  • Author(s): 谷口委代、鈴江一友、今井孝、下川周子、Olia Alex、久枝一
  • Organizer: 第87回日本寄生虫学会大会
• [Presentation] ウガンダ国の熱帯熱マラリア患者において腸内細菌叢の変化が起こる (2017)
  • Author(s): 谷口委代、宮内栄治、Olia Alex、長安英治、Osbert Katuro、鈴江一友、今井孝、下川周子、大西里咲、Odongo-Aginya E.I.、Palacpac Niriann、丸山治彦、木村英作、美田敏宏、大野博司、堀井俊宏、久枝一
  • Organizer: 第86回日本寄生虫学会大会
  • Place of Presentation: 北海道大学（北海道・札幌市）
  • Year and Date: 2017-05-28
• [Presentation] Altered gut microbiota composition in Plasmodium falciparum patients in Uganda (2017)
  • Author(s): Taniguchi T, Miyauchi E, Nakamura S, Hirai M, Suzue K, Imai T, Nomura T, Handa T, Okada H, Shimokawa C, Onishi R, Olia A, Hirata J, Tomita H, Ohno H, Horii T and Hisaeda H
  • Organizer: Japanese-Brazil Malaria Workshop 2017
  • Place of Presentation: サンパウロ（ブラジル）
  • Year and Date: 2017-03-15
  • Int'l Joint Research
• [Presentation] ウガンダ国の熱帯熱マラリア患者において腸内細菌叢の変化が起こる (2017)
  • Author(s): 谷口委代、宮内栄治、Olia Alex、長安英治、Osbert K、鈴江一友、今井孝、下川周子、大西里咲、Odongo-Aginya E.I., Palacpac Niriann、丸山治彦、木村英作、美田敏宏、大野博司、堀井俊宏、久枝一
  • Organizer: グローバルヘルス合同大会
• [Presentation] Altered gut microbiota composition in Plasmodium falciparum patients in Uganda (2017)
  • Author(s): Taniguchi T, Miyauchi E, Olia A, Nagayasu E, Osbert K, Suzue K, Imai T, Shimokawa C, Onishi R, Odongo-Aginya E.I., Palacpac Niriann, Maruyama H, Kimura E, Mita T, Ohno H, Horii T and Hisaeda H
  • Organizer: The American Society of Tropical Medicine and Hygiene 66th Annual Meeting
  • Int'l Joint Research
• [Presentation] ウガンダ国の熱帯熱マラリア患者において腸内細菌叢の変化が起こる (2017)
  • Author(s): 谷口委代、宮内栄治、Olia Alex、長安英治、Osbert K、鈴江一友、今井孝、下川周子、大西里咲、Odongo-Aginya E.I., Palacpac Niriann、丸山治彦、木村英作、美田敏宏、大野博司、堀井俊宏、久枝一
  • Organizer: 第86回日本寄生虫学会大会
• [Presentation] Plasmodium berghei ANKA infection induces intestinal dysbiosis (2016)
  • Author(s): Taniguchi T, Miyauchi E, Nakamura S, Hirai M, Suzue K, Imai T, Nomura T, Handa T, Okada H, Shimokawa C, Onishi R, Olia A, Hirata J, Tomita H, Ohno H, Horii T and Hisaeda H
  • Organizer: International Congress of Immunology
  • Place of Presentation: メルボルン（オーストラリア）
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] 、Pathogen non-specific bystander T cells were attenuated upon infection with malaria parasites (2016)
  • Author(s): Suzue K, Amano H, Taniguchi T, Shimokawa C, Olia A, Onishi R, and Hisaeda H
  • Organizer: International Congress of Immunology
  • Place of Presentation: メルボルン（オーストラリア）
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Plasmodium falciparum malaria alters the composition of intestinal microbiota in Ugandan patients (2016)
  • Author(s): Taniguchi T, Miyauchi E, Olia A, Nagayasu E, Sakurai M, Ikeda M, Imai T, Shimokawa C, Hirata J, Odongo-Aginya EI, Palacpac N, Maruyama H, Kimura E, Mita T, Ohno H, Horii T and Hisaeda H
  • Organizer: TICAD VI Pre-event; The 3rd International Symposium for the Promotion of Science and Technology Innovation Cooperation between Africa and Japan
  • Place of Presentation: JICA Ichigaya Building（東京都・本村町）
  • Int'l Joint Research
• [Book] 腸内細菌を含む新規宿主-マラリア原虫相互作用の解明 (2019)
  • Author(s): 谷口委代
  • Total Pages: 4
  • Publisher: 公益財団法人 大山健康財団
• [Remarks] ぐんまダイバーシティ推進地域ネットワーク 女性研究者シーズ集
  • URL: http://gunma-diversity.gunma-u.ac.jp/seeds_contents/taniguchi-tomoyo/
• [Remarks] 群馬大学大学院医学系研究科国際寄生虫病学
  • URL: http://www.med.gunma-u.ac.jp/med-organization/envmed/envmed-defense/157.html/
• [Remarks] 「ぐんまダイバーシティ推進地域ネットワーク」女性研究者シーズ集
  • URL: http://gunma-diversity.gunma-u.ac.jp/seeds_contents/taniguchi-tomoyo/