Clarifying the function of gut microbial message molecules and their association with cardiovascular diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03676
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kobe University
• Principal Investigator: Hirata Ken-ichi 神戸大学, 医学研究科, 教授 (20283880)
• Co-Investigator(Kenkyū-buntansha): 吉田 尚史 神戸大学, 医学研究科, 医学研究員 (00846321)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腸内細菌 / メッセージ物質 / 動脈硬化 / 炎症 / LPS / 外膜小胞 / 好中球細胞外トラップ

Outline of Final Research Achievements

We succeeded in isolating LPS and OMVs, which are message substances derived from gut bacteria. Both of them hardly migrated from the gut tract to the blood when administered orally or enterally to mice. The LPS activity of Bacteroides, which was identified as an atherosclerosis-preventing bacterium, was measured to be about 1/10 of that of Escherichia coli-derived LPS, indicating that it is very weakly inflammatory. We investigated the aggravating effect of intraperitoneal LPS administration on atherosclerosis in mice and clarified its mechanism. Neutrophil extracellular traps (NETs) at several days after the LPS injection and following macrophage chemokine production were observed in mouse atherosclerotic lesions. These are novel mechanisms that LPS activates inflammation and atherosclerosis.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

腸内細菌が産生するメッセージ物質の生体への影響を検証することで、注目される腸内細菌叢と動脈硬化との関連性を調査した研究である。腸内細菌の外膜小胞がほとんど腸管から血液中に移行しないことが発見できた。炎症を増悪すると考えられているLPSの生体作用を検証し、弱毒型の証明や、遅延型の炎症増悪機序を示すことができたことは、今後の研究に活かせて、腸内細菌を介する炎症に対する制御治療法の提案につながると考えている。