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

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08150
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Sapporo 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
• 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

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.

Free Research Field

間質性肺疾患

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。