Aiming for new treatment of heart failure through control of intestinal epithelial barrier function

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17141
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Saga-Kamo Akiko (嵯峨亜希子) 東京大学, 医学部附属病院, 届出研究員 (70867770)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 心不全 / 腸上皮バリア

Outline of Final Research Achievements

The purpose of this study is to elucidate the effects of regulation of intestinal epithelial barrier function on heart failure and to identify potential new gut-mediated therapies for heart failure.
In this study, I analyzed the intestinal epithelium and mucus layer of mice model of heart failure at the molecular and tissue levels, and examined how improving the intestinal epithelial barrier function affected heart failure. In the heart failure model mice fed dietary fiber, which is metabolized by the gut microbiota into short-chain fatty acids (mainly butyrate, propionate, and acetate) with anti-inflammatory effects, the decreases in the expression of antimicrobial peptides were suppressed, confirming the improvement of the gut epithelial barrier function. Furthermore, compared to the heart failure model group fed a normal diet, a trend toward improvement in cardiac function was observed.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

様々な心疾患の最終的な病態である心不全の患者数は世界的にみても近年急速に増加傾向にあり、さらなる病態解明および新たな治療、つまり心筋のみを標的とした研究だけではなく心臓と他臓器との臓器連関ネットワークを基にした新たな治療戦略が求められてきている。本研究によって腸上皮バリア機能の制御が心不全に及ぼす影響が明らかとなれば、腸を介した新たな心不全治療の可能性が見いだせる。