Evaluating the role of the lung microbiome in pulmonary fibrosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08175
• 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: Mie University
• Principal Investigator: NAKAHARA Hiroki 三重大学, 医学部附属病院, 助教 (30757092)
• Co-Investigator(Kenkyū-buntansha): 小林 哲 三重大学, 医学部附属病院, 准教授 (20437114) ; Gabazza Esteban 三重大学, 医学系研究科, 教授 (00293770)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: IPF / fibrosis / microbiome

Outline of Final Research Achievements

In the present investigation we developed a genetically engineered mouse model that expresses specifically in the lung the full-length of the human TGF-β1 gene. The mouse model spontaneously develops chronic pulmonary fibrosis. We evaluated the role of the lung microbiome in pulmonary fibrosis using this mouse model. We discovered that the fibrotic lung tissue has high concentration of salt and that bacteria of the Staphylococcus genera that grow when the fibrotic lung tissue is cultured under hypersaline conditions secrete a pro-apoptotic peptide. This peptide induces apoptosis of alveolar epithelial cell lines in vitro and promotes the death of alveolar epithelial cells in the transgenic mouse of pulmonary fibrosis. Overall, the results of this investigation showed that a bacterium from the lung microbiome secretes a deadly peptide that causes apoptosis of lung alveolar cells. This novel peptide may be a good target for the development of a novel therapy for pulmonary fibrosis.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

呼吸器疾患に関する細菌叢の検討は報告数も少なく、研究は始まったばかりである。呼吸器疾患の中で特発性肺線維症は悪性腫瘍と比較しても予後不良な難治性肺疾患である。本研究は肺の線維化の発症および進展を含めた病態への細菌叢の役割を明らかにするものであり、その機構が明らかになれば臨床応用にも期待がもてる画期的な研究である。今回の研究で同定されたブドウ球菌から分泌されるペプチドは肺線維症におけるアポトーシスに関与している可能性があり、新たなバイオマーカーの開発や治療標的となりうると考えられる。