Elucidation of disease control mechanism by intestinal bacteria-host interactions through extracellular phospholipid metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07042
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: MIKI Yoshimi 東京大学, 大学院医学系研究科(医学部), 特任研究員 (00632499)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 脂質 / ホスホリパーゼA2 / 腸内細菌 / 免疫 / がん / アレルギー / 炎症 / リポクオリティ

Outline of Final Research Achievements

Secretory phospholipase A2 (sPLA2) is the enzyme that has various physiological functions by metabolizing phospholipids in microenvironment of tissue where characteristically expressed in vivo. In this study, we focused on sPLA2-IIA, and attempted to elucidate the mechanism that sPLA2-IIA-deficient mice show exceptional phenotypes of cancer and allergy in remote tissues (skin) rather than in the site of expression (intestinal tract). Then, we found that sPLA2-IIA directly affected intestinal microbiota, the source of phospholipids in the intestinal tract, and altered the composition of intestinal microbiota and bacteria-specific lipid metabolites. These results elucidate a novel disease control mechanism via regulation of the intestinal microbiome by sPLA2, and expected to be applied to novel therapeutic and preventive strategies for various immune-related diseases.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、従来の脂質メディエーター動員酵素としてのPLA2の概念とは一線を画す脂質代謝酵素の新しい動作原理を提示したとともに、腸内細菌叢の研究領域にPLA2という新しい概念を導入した点で、独創的かつ創造的であると考えられる。sPLA2-IIAによる腸内細菌と細菌由来の代謝物の変化を定性的・定量的に捉えることに成功した本研究成果は、将来的に癌やアレルギー性疾患の発症や予後を予測するための新規診断法の開発や、当該代謝物を利用した創薬への展開も期待できる。