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Elucidation of the pathophysiology of acute exacerbation of IPF based on lung microbiome analysis and development of innovative treatment strategies

Research Project

Project/Area Number 18K08150
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionSapporo Medical University

Principal Investigator

Chiba Hirofumi  札幌医科大学, 医学部, 准教授 (40347175)

Co-Investigator(Kenkyū-buntansha) 齋藤 充史  札幌医科大学, 医学部, 助教 (00768939)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords特発性肺線維症 / マイクロバイオーム / 急性増悪 / 自然免疫 / ディスバイオシス / ディスバイオーシス / 肺サーファクタント蛋白質
Outline of Final Research Achievements

The presence of a diverse microbiome has also been revealed in the lower respiratory tract, which has been considered sterile. Applicants focus on IPF. A microbiome analysis in the patient's BALF was performed. The results showed that (1) loss of microbiome diversity correlates with mortality, and (2) growth of specific bacterial groups correlates with disease progression. On the other hand, the relationship between the onset of acute exacerbations and the transformation of the microbiome could not be shown due to the small number of events. This is a continuing issue for the future. In a mouse bleomycin administration model, it was revealed that the microbiome showed changes similar to IPF. In the future, this model will also be used to elucidate the pathophysiology and examine treatment strategies.

Academic Significance and Societal Importance of the Research Achievements

IPFの病態に肺内マイクロバイオームが関連することが示され、これら菌体成分のTOll様受容体等、パターン認識受容体を介した自然免疫応答等が本症でも重要な検討領域になると考えられる。本研究により、今後の研究に対する方向性を示すことができた。また、マウスのブレオマイシン投与肺線維症モデルの肺内マイクロバイオームがヒトIPF患者の肺内マイクロバイオームと近似していることを示せたことは、今後、同モデルを用いることにより、IPFの病態の解明、マイクロバイオームに焦点を当てた治療戦略の検討が簡便となった。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (4 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis2020

    • Author(s)
      Yoshikawa Takumi、Otsuka Mitsuo、Chiba Hirofumi、Ikeda Kimiyuki、Mori Yuki、Umeda Yasuaki、Nishikiori Hirotaka、Kuronuma Koji、Takahashi Hiroki
    • Journal Title

      BMC Pulmonary Medicine

      Volume: 20 Issue: 1 Pages: 2727-2727

    • DOI

      10.1186/s12890-020-1060-y

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant populations of circulating T follicular helper cells and regulatory B cells underlying idiopathic pulmonary fibrosis2019

    • Author(s)
      Asai Yuichiro、Chiba Hirofumi、Nishikiori Hirotaka、Kamekura Ryuta、Yabe Hayato、Kondo Shun、Miyajima Satsuki、Shigehara Katsunori、Ichimiya Shingo、Takahashi Hiroki
    • Journal Title

      Respiratory Research

      Volume: 20 Issue: 1 Pages: 244-244

    • DOI

      10.1186/s12931-019-1216-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired diversity of the lung microbiome predicts progression of idiopathic pulmonary fibrosis2018

    • Author(s)
      Takahashi Youhei、Saito Atsushi、Chiba Hirofumi、Kuronuma Koji、Ikeda Kimiyuki、Kobayashi Tomofumi、Ariki Shigeru、Takahashi Motoko、Sasaki Yasushi、Takahashi Hiroki
    • Journal Title

      Respir Res

      Volume: 19 Issue: 1 Pages: 34-34

    • DOI

      10.1186/s12931-018-0736-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Clinical significance of serum SP-D as a biomarker for antifibrotics in idiopathic pulmonary fibrosis (IPF): Post hoc analysis of a phase 3 trial of pirfenidone in Japan2019

    • Author(s)
      Hirofumi Chiba
    • Organizer
      European Respiratory Society Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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