Gut butyrate-producers confer post-infarction cardiac protection
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43167-5 |
| _version_ | 1797630101424177152 |
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| author | 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 Patrick C. H. Hsieh |
| author_facet | 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 Patrick C. H. Hsieh |
| author_sort | Hung-Chih Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T11:03:13Z |
| format | Article |
| id | doaj.art-6361bc3495944b3fb58bc006af3e56af |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T11:03:13Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6361bc3495944b3fb58bc006af3e56af2023-11-12T12:23:32ZengNature PortfolioNature Communications2041-17232023-11-0114111610.1038/s41467-023-43167-5Gut butyrate-producers confer post-infarction cardiac protectionHung-Chih Chen0Yen-Wen Liu1Kuan-Cheng Chang2Yen-Wen Wu3Yi-Ming Chen4Yu-Kai Chao5Min-Yi You6David J. Lundy7Chen-Ju Lin8Marvin L. Hsieh9Yu-Che Cheng10Ray P. Prajnamitra11Po-Ju Lin12Shu-Chian Ruan13David Hsin-Kuang Chen14Edward S. C. Shih15Ke-Wei Chen16Shih-Sheng Chang17Cindy M. C. Chang18Riley Puntney19Amy Wu Moy20Yuan-Yuan Cheng21Hsin-Yuan Chien22Jia-Jung Lee23Deng-Chyang Wu24Ming-Jing Hwang25Jennifer Coonen26Timothy A. Hacker27C-L. Eric Yen28Federico E. Rey29Timothy J. Kamp30Patrick C. H. Hsieh31Institute of Biomedical Sciences, Academia SinicaDivision of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDivision of Cardiovascular Medicine, China Medical University HospitalCardiovascular Medical Center, Far Eastern Memorial HospitalInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaGraduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical UniversityInstitute of Biomedical Sciences, Academia SinicaModel Organisms Research Core, Department of Medicine, University of Wisconsin-MadisonInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaDivision of Cardiovascular Medicine, China Medical University HospitalDivision of Cardiovascular Medicine, China Medical University HospitalModel Organisms Research Core, Department of Medicine, University of Wisconsin-MadisonWisconsin National Primate Research Center, University of Wisconsin–MadisonWisconsin National Primate Research Center, University of Wisconsin–MadisonInstitute of Biomedical Sciences, Academia SinicaInstitute of Biomedical Sciences, Academia SinicaDivision of Nephrology, Department of Medicine, Kaohsiung Medical University & HospitalDivision of Gastroenterology, Department of Medicine, Kaohsiung Medical University & HospitalInstitute of Biomedical Sciences, Academia SinicaWisconsin National Primate Research Center, University of Wisconsin–MadisonModel Organisms Research Core, Department of Medicine, University of Wisconsin-MadisonInstitute of Biomedical Sciences, Academia SinicaDepartment of Bacteriology, University of Wisconsin-MadisonDepartment of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-MadisonInstitute of Biomedical Sciences, Academia SinicaAbstract 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.https://doi.org/10.1038/s41467-023-43167-5 |
| spellingShingle | 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 Patrick C. H. Hsieh Gut butyrate-producers confer post-infarction cardiac protection Nature Communications |
| title | Gut butyrate-producers confer post-infarction cardiac protection |
| title_full | Gut butyrate-producers confer post-infarction cardiac protection |
| title_fullStr | Gut butyrate-producers confer post-infarction cardiac protection |
| title_full_unstemmed | Gut butyrate-producers confer post-infarction cardiac protection |
| title_short | Gut butyrate-producers confer post-infarction cardiac protection |
| title_sort | gut butyrate producers confer post infarction cardiac protection |
| url | https://doi.org/10.1038/s41467-023-43167-5 |
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