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 PuntneyAmy 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, Patrick C.H. Hsieh

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article number7249
JournalNature communications
Volume14
Issue number1
DOIs
Publication statusPublished - 2023 Dec

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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