Gut butyrate-producers confer post-infarction cardiac protection

Hung-Chih Chen, Yen-Wen Liu, Kuan-Cheng Chang, Yen-Wen Wu, Yi-Ming Chen, Yu-Kai Chao, Min-Yi You, David J. Lundy, Chen-Ju Lin, Marvin L. Hsieh, Yu-Che Cheng, Ray P. Prajnamitra, Po-Ju Lin, Shu-Chian Ruan, David Hsin-Kuang Chen, Edward S. C. Shih, Ke-Wei Chen, Shih-Sheng Chang, Cindy M. C. Chang, Riley Puntney, Amy Wu Moy, Yuan-Yuan Cheng, Hsin-Yuan Chien, Jia-Jung Lee, Deng-Chyang Wu, Ming-Jing Hwang, Jennifer Coonen, Timothy A. Hacker, C-L. Eric Yen, Federico E. Rey, Timothy J. Kamp and Patrick C. H. Hsieh ()
Additional contact information
Hung-Chih Chen: Academia Sinica
Yen-Wen Liu: National Cheng Kung University
Kuan-Cheng Chang: China Medical University Hospital
Yen-Wen Wu: Far Eastern Memorial Hospital
Yi-Ming Chen: Academia Sinica
Yu-Kai Chao: Academia Sinica
Min-Yi You: Academia Sinica
David J. Lundy: Taipei Medical University
Chen-Ju Lin: Academia Sinica
Marvin L. Hsieh: University of Wisconsin-Madison
Yu-Che Cheng: Academia Sinica
Ray P. Prajnamitra: Academia Sinica
Po-Ju Lin: Academia Sinica
Shu-Chian Ruan: Academia Sinica
David Hsin-Kuang Chen: Academia Sinica
Edward S. C. Shih: Academia Sinica
Ke-Wei Chen: China Medical University Hospital
Shih-Sheng Chang: China Medical University Hospital
Cindy M. C. Chang: University of Wisconsin-Madison
Riley Puntney: University of Wisconsin–Madison
Amy Wu Moy: University of Wisconsin–Madison
Yuan-Yuan Cheng: Academia Sinica
Hsin-Yuan Chien: Academia Sinica
Jia-Jung Lee: Kaohsiung Medical University & Hospital
Deng-Chyang Wu: Kaohsiung Medical University & Hospital
Ming-Jing Hwang: Academia Sinica
Jennifer Coonen: University of Wisconsin–Madison
Timothy A. Hacker: University of Wisconsin-Madison
C-L. Eric Yen: Academia Sinica
Federico E. Rey: University of Wisconsin-Madison
Timothy J. Kamp: University of Wisconsin-Madison
Patrick C. H. Hsieh: Academia Sinica

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.

Date: 2023
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DOI: 10.1038/s41467-023-43167-5

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