심우섭 (가톨릭대학교 의과대학)

한빛사논문

조회297

가톨릭대학교 의과대학

Cardiovasc. Res., Jun 08 2024, cvae128 | https://doi.org/10.1093/cvr/cvae128 Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischemic heart disease

Quynh Hoa Pham ^1,2,5, Thi Van Anh Bui ^1,2,5, Woo-Sup Sim ^3,4,5, King Hoo Lim ^1,2, Carmen Oi Kwan Law ^1,2, Wanyu Tan ^1,2, Ri Youn Kim ^1,2, Kwan Ting Chow ^1,2, Hun-Jun Park ^3,4, Kiwon Ban ^1,2, Terrence Chi Kong Lau^1,2

¹Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong Special Administrative Region.

²Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong Special Administrative Region.

³Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, Korea.

⁴Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, Korea.

⁵These authors contributed equally.

Quynh Hoa Pham, Thi Van Anh Bui and Woo-Sup Sim contributed equally to this work.

Correspondence should be addressed to Terrence Chi Kong Lau, Kiwon Ban, Hun-Jun Park, Kwan Ting Chow

Abstract

Given the extremely limited regeneration potential of the heart, one of the most effective strategies to reduce the prevalence and mortality of coronary artery disease is prevention. Short-chain fatty acids (SCFAs), which are by-products of beneficial probiotics, have been reported to possess cardioprotective effects. Despite their beneficial roles, delivering SCFAs and maintaining their effective concentration in plasma present major challenges. Therefore, in the present study, we aimed to devise a strategy to prevent coronary heart disease effectively by using engineered probiotics to continuously release SCFAs in vivo. We engineered a novel probiotic cocktail, EcN_TL, from the commercially available Escherichia coli Nissle 1917 strain to continuously secrete SCFAs by introducing the propionate and butyrate biosynthetic pathways. Oral administration of EcN_TL enhanced and maintained an effective concentration of SCFAs in the plasma. As a preventative strategy, we observed that daily intake of EcN_TL for 14 days prior to ischemia-reperfusion injury significantly reduced myocardial injury and improved cardiac performance compared to EcN administration. We uncovered that EcN_TL's protective mechanisms included reducing neutrophil infiltration into the infarct site and promoting the polarization of wound-healing macrophages. We further revealed that SCFAs at plasma concentration protected cardiomyocytes from inflammation by suppressing the NF-κB activation pathway. These data provide strong evidence to support the use of SCFA-secreting probiotics to prevent coronary heart disease. Since SCFAs also play a key role in other metabolic diseases, EcN_TL can potentially be used to treat a variety of other diseases.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-10)
연구진국내(교신)+국외 연구진
분야 의약학 > 재생의학

댓글 작성 로그인

CV 열람하기

연락처 보기