Analyses of interaction between malaria and intestinal microbiota in patients in Uganda

• Project/Area Number: 15H05274
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: National Institute of Infectious Diseases (2016-2018); Gunma University (2015)
• Principal Investigator: Hisaeda Hajime 国立感染症研究所, 寄生動物部, 部長 (50243689)
• Research Collaborator: Ohno Hiroshi ; Miyauchi Eiji ; Emmanuel Odongo-Aginya ; Olia Alex ; Ogwang Martin
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: マラリア / ウガンダ / 腸内細菌 / 腸管内寄生虫

Outline of Final Research Achievements

We collected more than 300 blood and fecal samples from malaria patients in Uganda from 2015 to 2016 and comprehensively analyzed fecal microbiota. Malaria patients have altered microbiota including change in enterotype compared with non-malarial healthy volunteers, and the degree in alteration was much higher in patients with severe malaria. The microbiota in those patients after treatment became closer to healthy controls. These results indicate that malaria, especially severe malaria affects intestinal microbiota. We also analyzed inflammatory proteins such as cytokines in plasma samples and found some proteins remarkably increased or decreased in severe malaria patients.

Academic Significance and Societal Importance of the Research Achievements

これまで知られていなかったマラリアと腸内細菌の相互作用によるマラリアの病態形成の一端を明らかにできた。プロバイオティクスによる腸内環境の整備が新たな抗マラリア戦略の基盤となることが期待される。また、腸内細菌叢の変化とそれにともなう免疫応答の変調の解明、細菌叢の是正による免疫の正常化手段の確立も考えられ、炎症性疾患の新たな治療法、予防法の確立の確実な足がかりなることも期待できる。

Research Products

• [Int'l Joint Research] Gulu University/St Mary's Lacor Hospital(ウガンダ)
• [Int'l Joint Research] Technion(イスラエル)
• [Int'l Joint Research] グル大学医学部/ラチョー病院(ウガンダ)
• [Int'l Joint Research] グル大学医学部/ラチョー病院(ウガンダ)
• [Journal Article] Suppression of obesity by an intestinal helminth through interactions with intestinal microbiota. (2019)
  • Author(s): Shimokawa C, Obi S, Shibata M, Olia A, Imai T, Suzue K, Hisaeda H.
  • Journal Title: Infection and Immunity Volume: 印刷中 Issue: 6
  • DOI: 10.1128/iai.00042-19
  • Peer Reviewed / Open Access
• [Journal Article] Escherichia coli mediated resistance of Entamoeba histolytica to oxidative stress is triggered by oxaloacetate. (2018)
  • Author(s): Shaulov Y, Shimokawa C, Trebicz-Geffen M, Nagaraja S, Methling K, Lalk M, Weiss-Cerem L, Lamm AT, Hisaeda H, Ankri S.
  • Journal Title: PLoS Pathongen Volume: 14 Issue: 10 Pages: e1007295-e1007295
  • DOI: 10.1371/journal.ppat.1007295
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intestinal Inflammation-Mediated Clearance of Amebic Parasites Is Dependent on IFN-γ (2018)
  • Author(s): Shimokawa C, Senba M, Kobayashi S, Kikuchi M, Obi S, Olia A, Hamano S, Hisaeda H
  • Journal Title: Journal of Immunology Volume: 200 Issue: 3 Pages: 1101-1109
  • DOI: 10.4049/jimmunol.1700806
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mast Cells Are Crucial for Induction of Group 2 Innate Lymphoid Cells and Clearance of Helminth Infections. (2017)
  • Author(s): Shimokawa C, Kanaya T, Hachisuka M, Ishiwata K, Hisaeda H, Kurashima Y, Kiyono H, Yoshimoto T, Kaisho T, Ohno H.
  • Journal Title: Immunity Volume: 46 Issue: 5 Pages: 863-874
  • DOI: 10.1016/j.immuni.2017.04.017
  • 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] Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis (2015)
  • 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, Hisaeda H
  • Journal Title: Scientific Reports Volume: 5:15699 Issue: 1 Pages: 1-12
  • DOI: 10.1038/srep15699
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A transient resistance to blood-stage malaria in interferon-γ-deficient mice through impaired production of host cells preferred by malaria parasites (2015)
  • Author(s): Okada H, Suzue K, Imai T, Taniguchi T, Shimokawa C, Onishi R, Hirata J, and Hisaeda H
  • Journal Title: Frontiers in Microbiology Volume: 6:600 Pages: 1-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Book] 人獣共通感染症 (2016)
  • Author(s): 久枝一
  • Total Pages: 6
  • Publisher: 医薬ジャーナル社
• [Patent(Industrial Property Rights)] 制御性Ｔ細胞増強剤並びにそれを含む医薬及び食品組成物 (2017)
  • Inventor(s): 久枝一、下川周子、和泉孝志、大嶋紀安、大野博司、加藤完
  • Industrial Property Rights Holder: 久枝一、下川周子、和泉孝志、大嶋紀安、大野博司、加藤完
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-094949
  • Filing Date: 2017