<i>Flavonifractor Plautii</i> or Its Metabolite Desaminotyrosine as Prophylactic Agents for Alleviating Myocardial Ischemia/Reperfusion Injury
Myocardial ischemia/reperfusion (I/R) injury is a major contributor to myocardial damage, leading to adverse cardiac remodeling and dysfunction. Recent studies have highlighted the potential of gut microbiota-derived metabolites in modulating cardiac outcomes. Here, the cardioprotective effects of a commensal bacterium Flavonifractor plautii (F. plautii) and its metabolite desaminotyrosine (DAT) against myocardial I/R injury are investigated. We showed that prophylactic gavage of F. plautii attenuates myocardial I/R injury as evidenced by improved cardiac function and reduced cardiac injury. We also found that its metabolite DAT recapitulates these cardioprotective effects against myocardial I/R injury. Transcriptomic analysis has revealed that DAT preserves cardiac tissue and attenuates immune responses against myocardial I/R injury. Mechanistically, DAT promotes cardiomyocyte survival through the modulation of the nicotinamide adenine dinucleotide phosphate (NADP<sup>+</sup>/NADPH) ratio. Further, DAT suppressed macrophage proinflammatory activities and cardiac inflammation via the reduction in interleukin-6 (IL-6) production. Taken together, our findings indicate that F. plautii and its metabolite DAT exert pleiotropic cardioprotective effects against myocardial I/R injury, suggesting them as potential prophylactic therapeutic options for alleviating myocardial I/R injury.
Authors
- Jiahe Zhang
- Jiawan Wang (ORCID: https://orcid.org/0000-0002-2199-0483)
- Yuan Hai-long (ORCID: https://orcid.org/0009-0006-3930-525X)
- Moshi Song (ORCID: https://orcid.org/0000-0001-9929-8975)
- Qi Gu
- Jianghua Shen (ORCID: https://orcid.org/0000-0003-1017-0698)
- Pengfei Xu (ORCID: https://orcid.org/0000-0002-0389-1182)
- Heng Du (ORCID: https://orcid.org/0009-0006-1950-9650)
- Zeyu Gao (ORCID: https://orcid.org/0000-0003-2365-8318)
- Chaofan Yang
- Fang Wang (ORCID: https://orcid.org/0000-0001-9986-0948)
- Jun Wang (ORCID: https://orcid.org/0000-0002-8859-7707)
- Siqi Liu (ORCID: https://orcid.org/0000-0001-9744-3681)
- Yujing Li (ORCID: https://orcid.org/0000-0002-1963-3188)
- Xu Liu (ORCID: https://orcid.org/0000-0002-5107-1074)
- Yanan Zhou (ORCID: https://orcid.org/0000-0002-8170-7811)
- Jingjing Lu (ORCID: https://orcid.org/0000-0001-8574-8824)
- Hao Zhang (ORCID: https://orcid.org/0000-0003-0704-050X)
- Tuo Wei (ORCID: https://orcid.org/0000-0002-2823-9721)
- Jian Zang (ORCID: https://orcid.org/0009-0001-1251-977X)
- Gan Xi
- Yuhan Wang (ORCID: https://orcid.org/0000-0001-6451-1166)
Institutions
- Chinese Academy of Sciences (CN)
- Beijing Chao-Yang Hospital, Capital Medical University (CN)
- University of Chinese Academy of Sciences (CN)
- Institute of Zoology (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-03-16
- DOI
- https://doi.org/10.1002/advs.202417827
- Citations
- 7
- Primary Topic
- Cardiac Ischemia and Reperfusion
- Type
- article
- Field-Weighted Citation Impact
- 10.30
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Beijing Municipality
- National Key Research and Development Program of China