Flavonifractor Plautii or Its Metabolite Desaminotyrosine as Prophylactic Agents for Alleviating Myocardial Ischemia/Reperfusion Injury

  • Adv Sci (Weinh). 2025 Jun;12(21):e2417827. doi: 10.1002/advs.202417827.
Heng Du  1  2 ,  Xu Liu  1  2 ,  Jianghua Shen  1  2 ,  Hailong Yuan  1  2 ,  Hao Zhang  1  2 ,  Gan Xi  2  3 ,  Yujing Li  1  2  4  5 ,  Yuhan Wang  1  2  4  5 ,  Jiahe Zhang  1  2  4  5 ,  Chaofan Yang  1  2  4  5 ,  Pengfei Xu  1  2  4  5 ,  Jiawan Wang  6 ,  Fang Wang  1  4 ,  Siqi Liu  1  2  4  5 ,  Yanan Zhou  1  2  4  5 ,  Qi Gu  1  2  4  5 ,  Jingjing Lu  2  3 ,  Tuo Wei  1  2  4  5 ,  Zeyu Gao  1  5 ,  Jingyi Zang  1  5 ,  Jun Wang  2  3 ,  Moshi Song  1  2  4  5
Affiliations
  • 1. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 2. University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 4. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
  • 5. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
  • 6. Department of Anesthesiology, Beijing Chao-Yang Hospital, Beijing, 100020, China.
PMID: 40089859 DOI: 10.1002/advs.202417827
Abstract

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+/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.

Keywords
Flavonifractor plautii; cardiac inflammation; cardiomyocyte survival; desaminotyrosine; myocardial ischemia/reperfusion injury.
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