Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease

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

doi:10.1093/cvr/cvae128

Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease

Quynh Hoa Pham (Co-first Author), Thi Van Anh Bui (Co-first Author), Woo-Sup Sim (Co-first Author), King Hoo Lim, Carmen Oi Kwan Law, Wanyu Tan, Ri Youn Kim, Kwan Ting Chow^*, Hun-Jun Park^*, Kiwon Ban^*, Terrence Chi Kong Lau^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

13 Citations (Scopus)

29 Downloads (CityUHK Scholars)

Abstract

AIM: 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.

Methods and results: 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.

Conclusions: 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.

Original language	English
Pages (from-to)	1737-1751
Journal	Cardiovascular Research
Volume	120
Issue number	14
Online published	8 Jun 2024
DOIs	https://doi.org/10.1093/cvr/cvae128
Publication status	Published - Oct 2024

Funding

This research was funded by the following funding: Research Grants Council, University Grants Committee (CityU 11102122 to T.C.K.L.), Health and Medical Research Fund, Food and Health Bureau, Hong Kong (20190932 to TCKL), Tung Biomedical Sciences Centre, City University of Hong Kong (to K.T.C., T.C.K.L., and K.W.B.); Croucher Foundation (9509002 to K.T.C.), and National Research Foundation of Korea (grant numbers RS-2023-00219981 to K.W.B. and RS-2023-00220207 to H.-J.P.).

Research Keywords

Coronary heart disease
Myocardial infarction
Prevention
Probiotics
Short-chain fatty acid

Publisher's Copyright Statement

This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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RGC-funded

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/cvr/cvae128

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Pham, Q. H., Bui, T. V. A., Sim, W.-S., Lim, K. H., Law, C. O. K., Tan, W., Kim, R. Y., Chow, K. T., Park, H.-J., Ban, K., & Lau, T. C. K. (2024). Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease. Cardiovascular Research, 120(14), 1737-1751. https://doi.org/10.1093/cvr/cvae128

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title = "Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease",

abstract = "AIM: 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.Methods and results: 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.Conclusions: 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.{\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.",

keywords = "Coronary heart disease, Myocardial infarction, Prevention, Probiotics, Short-chain fatty acid",

author = "Pham, {Quynh Hoa} and Bui, {Thi Van Anh} and Woo-Sup Sim and Lim, {King Hoo} and Law, {Carmen Oi Kwan} and Wanyu Tan and Kim, {Ri Youn} and Chow, {Kwan Ting} and Hun-Jun Park and Kiwon Ban and Lau, {Terrence Chi Kong}",

note = "{\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2024",

month = oct,

doi = "10.1093/cvr/cvae128",

language = "English",

volume = "120",

pages = "1737--1751",

journal = "Cardiovascular Research",

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Pham, QH, Bui, TVA, Sim, W-S, Lim, KH, Law, COK, Tan, W, Kim, RY, Chow, KT, Park, H-J, Ban, K & Lau, TCK 2024, 'Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease', Cardiovascular Research, vol. 120, no. 14, pp. 1737-1751. 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 ischaemic heart disease. / Pham, Quynh Hoa (Co-first Author); Bui, Thi Van Anh (Co-first Author); Sim, Woo-Sup (Co-first Author) et al.
In: Cardiovascular Research, Vol. 120, No. 14, 10.2024, p. 1737-1751.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease

AU - Pham, Quynh Hoa

AU - Bui, Thi Van Anh

AU - Sim, Woo-Sup

AU - Lim, King Hoo

AU - Law, Carmen Oi Kwan

AU - Tan, Wanyu

AU - Kim, Ri Youn

AU - Chow, Kwan Ting

AU - Park, Hun-Jun

AU - Ban, Kiwon

AU - Lau, Terrence Chi Kong

PY - 2024/10

Y1 - 2024/10

N2 - AIM: 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.Methods and results: 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.Conclusions: 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.© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.

AB - AIM: 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.Methods and results: 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.Conclusions: 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.© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.

KW - Coronary heart disease

KW - Myocardial infarction

KW - Prevention

KW - Probiotics

KW - Short-chain fatty acid

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DO - 10.1093/cvr/cvae128

M3 - RGC 21 - Publication in refereed journal

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JO - Cardiovascular Research

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ER -

Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

UN SDGs

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GRF: Unraveling the Functional Roles of yafB in Metabolic Adaptation of Bacteria during Infection

HMRF: Dissecting the Functional Role of Prevalent Incompatible Group I1 Plasmid Isolated from Human and Animals in Hong Kong

CROU: Harnessing Plasmacytoid Dendritic Cells for Cancer Immunotherapy

Cite this

Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

UN SDGs

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

GRF: Unraveling the Functional Roles of yafB in Metabolic Adaptation of Bacteria during Infection

HMRF: Dissecting the Functional Role of Prevalent Incompatible Group I1 Plasmid Isolated from Human and Animals in Hong Kong

CROU: Harnessing Plasmacytoid Dendritic Cells for Cancer Immunotherapy

Cite this