Impact of gut microbial LPS on cardiovascular diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23944
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kobe University
• Principal Investigator: Yoshida Naofumi 神戸大学, 医学研究科, 医学研究員 (00846321)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 循環器疾患 / 腸内細菌 / リポ多糖

Outline of Final Research Achievements

Cardiovascular disease (CVD) is considered as an inflammatory disease. Thus, we aim to understand the novel inflammatory origin of CVD, and explore therapeutic approaches to directly regulate the source of inflammation. We previously reported that gut microbiota dysbiosis is related to coronary artery disease and heart failure. As gut bacterial lipopolysaccharide (LPS) acts as an important intermediary between the gut microbiota and immune cell activation, we hypothesized that it could have a pivotal role as an inflammatory origin in the development of CVD. We elucidated that each bacterial species has a distinct LPS structure, which are associated with differing immunogenicity. CVD patients have high immunogenicity LPS and fecal LPS levels in patients with CVD is higher than that of non-CVD patients. The atherosclerosis-prone mice injected LPS show worsening atherosclerosis. These results indicate that gut microbial LPS serve as a novel therapeutic approach to prevent CVD.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

これまで我々は、循環器疾患患者における特徴的な腸内細菌叢を明らかとしてきた。しかしこの腸内細菌叢の偏倚が、どのように循環器疾患の発症、進展に寄与しているのかについては未解明の部分が残されていた。本研究成果により、循環器疾患患者の腸内細菌由来の炎症惹起能の高いリポ多糖が、循環器疾患の発症、進展に関与している事が示唆された。この事から腸内細菌と循環器疾患を繋ぐ機序の一端が解明され、今後腸内細菌由来リポ多糖に着目した、新たな循環器疾患の予防、治療法の開発が期待される。