Gut butyrate-producers confer post-infarction cardiac protection
Journal
Nature communications
Journal Volume
14
Journal Issue
1
Date Issued
2023-11-09
Author(s)
Chen, Hung-Chih
Liu, Yen-Wen
Chang, Kuan-Cheng
Chen, Yi-Ming
Chao, Yu-Kai
You, Min-Yi
Lundy, David J
Lin, Chen-Ju
Hsieh, Marvin L
Cheng, Yu-Che
Prajnamitra, Ray P
Lin, Po-Ju
Ruan, Shu-Chian
Chen, David Hsin-Kuang
Shih, Edward S C
Chen, Ke-Wei
Chang, Shih-Sheng
Chang, Cindy M C
Puntney, Riley
Moy, Amy Wu
Cheng, Yuan-Yuan
Chien, Hsin-Yuan
Lee, Jia-Jung
Wu, Deng-Chyang
Hwang, Ming-Jing
Coonen, Jennifer
Hacker, Timothy A
Yen, C-L Eric
Rey, Federico E
Kamp, Timothy J
Hsieh, Patrick C H
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.
Type
journal article