Insight into the Molecular Mechanisms of Heart-Gut Axis in the Pathophysiology of Heart Failure

• Project/Area Number: 17K15989
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: The Institute for Adult Diseases Asahi Life Foundation
• Principal Investigator: Kamo Takehiro 公益財団法人朝日生命成人病研究所, 循環器科, 部長 (10722556)
• Research Collaborator: Yao Takako
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 心疾患 / 腸上皮バリア / 腸内細菌

Outline of Final Research Achievements

The aim of this research is to explore the link between the heart and the gut and to clarify the functional roles of the gut and the gut microbiota in the pathophysiology of heart failure. This research focuses on the following subjects.
1) Insight into the role of gut epithelial barrier function in heart failure. I have found that expression levels of antimicrobial peptides were decreased in the gut epithelium of mice with heart failure.
2) Insight into the functional role of gut microbiota in heart failure. I recently showed that heart failure is associated with gut microbiota dysbiosis through 16S ribosomal RNA gene sequencing of fecal samples from patients with heart failure. Furthermore, I have discovered that depletion of gut microbiota attenuates cardiac hypertrophy in mice with heart failure.

Academic Significance and Societal Importance of the Research Achievements

本研究によって腸および腸内細菌叢と心不全との関連性が明らかになれば、心不全の病態研究にブレイクスルーがもたらされ、さらに腸上皮バリアおよび腸内細菌叢への介入による新たな心不全治療開発の基盤構築につながることが期待される。すなわち、食事や薬剤などにより腸上皮バリアおよび腸内細菌叢を制御することができれば、これまでの薬物治療とは全く異なるアプローチによる心不全治療が確立されることになる。

Research Products

• [Journal Article] Novel Concept of a Heart-Gut Axis in the Pathophysiology of Heart Failure (2017)
  • Author(s): Takehiro Kamo, Hiroshi Akazawa, Jun-ichi Suzuki, Issei Komuro
  • Journal Title: Korean Circulation Journal Volume: 47 Issue: 5 Pages: 663-669
  • DOI: 10.4070/kcj.2017.0028
  • Peer Reviewed / Open Access
• [Journal Article] Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure. (2017)
  • Author(s): Kamo T, Akazawa H, Suda W, Saga-Kamo A, Shimizu Y, Yagi H, Liu Q, Nomura S, Naito AT, Takeda N, Harada M, Toko H, Kumagai H, Ikeda Y, Takimoto E, Suzuki JI, Honda K, Morita H, Hattori M, Komuro I.
  • Journal Title: PLoS One. Volume: 12 Issue: 3 Pages: 0174099-0174099
  • DOI: 10.1371/journal.pone.0174099
  • Peer Reviewed / Open Access
• [Presentation] Gut Microbiota Depletion Suppresses Isoproterenol-Induced Cardiac Hypertrophy in Mice (2019)
  • Author(s): Takehiro Kamo, Takako Yao
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] Depletion of Gut Microbiota Attenuates Cardiac Hypertrophy Induced by Isoproterenol in Mice (2018)
  • Author(s): Takako Yao, Takehiro Kamo
  • Organizer: American Heart Association Scientific Sessions 2018
  • Int'l Joint Research
• [Presentation] Gut Microbiota Depletion Alters Cardiac Hypertrophy in Mice (2018)
  • Author(s): Takehiro Kamo, Takako Yao
  • Organizer: 第2回日本循環器学会基礎研究フォーラム
• [Presentation] Dysbiosis and Compositional Alterations with Aging in the Gut Microbiota of Patients with Heart Failure (2017)
  • Author(s): Takehiro Kamo, Hiroshi Akazawa, Akiko Saga, Yu Shimizu, Hiroki Yagi, Qing Liu, Chizuru Yabumoto, Issei Komuro
  • Organizer: 第81回日本循環器学会学術集会
• [Remarks] 心不全について ～「心腸連関」から病態に迫る～
  • URL: http://www.asahi-life.or.jp/seizinbyou_news013.html