Loss of lung microbiome diversity and immune mechanisms of pulmonary surfactant proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08570
• 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: Kuronuma Koji 札幌医科大学, 医学部, 准教授 (40563250)
• Co-Investigator(Kenkyū-buntansha): 齋藤 充史 札幌医科大学, 医学部, 講師 (00768939) ; 千葉 弘文 札幌医科大学, 医学部, 教授 (40347175)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 肺サーファクタント / 自然免疫 / 肺マイクロバイオーム

Outline of Final Research Achievements

Microbiome analysis of mice fed a niacin-restricted diet revealed that they were in a state of dysbiosis. When pirfenidone was administered to niacin-deficient mice, pellagra-like symptoms were enhanced, and NNMT was the main contributing factor. Microbiome analysis of stool samples collected from COVID-19 patients revealed that more severely ill patients were in a state of dysbiosis, with a decrease in substances involved in tryptophan metabolism. We found that serum SP-A and SP-D were elevated in COVID-19 patients and associated with the severity of COVID-19 pneumonia.

Free Research Field

呼吸器病学、感染症学

Academic Significance and Societal Importance of the Research Achievements

マイクロバイオーム解析の手法によりナイアシン欠乏と嘔気嘔吐などの副作用を示す薬剤の関連を明らかにした。その主要因となる物質を特定したため、尿の測定により副作用予測に用いられる可能性がある。また、COVID-19患者のマイクロバイオーム解析でもより重症患者の方が菌の多様性が低下している状態であり、重症化機序の一部を示した。COVID-19肺炎では血清SP-AとSP-Dが重症度を評価するバイオマーカーとなりうる。