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

Heng Du; Xu Liu; Jianghua Shen; Hailong Yuan; Hao Zhang; Gan Xi; Yujing Li; Yuhan Wang; Jiahe Zhang; Chaofan Yang; Pengfei Xu; Jiawan Wang; Fang Wang; Siqi Liu; Yanan Zhou; Qi Gu; Jingjing Lu; Tuo Wei; Zeyu Gao; Jingyi Zang; Jun Wang; Moshi Song

doi:10.1002/advs.202417827

Advanced Science (Jun 2025)

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

Heng Du,
Xu Liu,
Jianghua Shen,
Hailong Yuan,
Hao Zhang,
Gan Xi,
Yujing Li,
Yuhan Wang,
Jiahe Zhang,
Chaofan Yang,
Pengfei Xu,
Jiawan Wang,
Fang Wang,
Siqi Liu,
Yanan Zhou,
Qi Gu,
Jingjing Lu,
Tuo Wei,
Zeyu Gao,
Jingyi Zang,
Jun Wang,
Moshi Song

Affiliations

Heng Du: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Xu Liu: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Jianghua Shen: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Hailong Yuan: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Hao Zhang: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Gan Xi: University of Chinese Academy of Sciences Beijing 100049 China
Yujing Li: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Yuhan Wang: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Jiahe Zhang: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Chaofan Yang: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Pengfei Xu: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Jiawan Wang: Department of Anesthesiology Beijing Chao‐Yang Hospital Beijing 100020 China
Fang Wang: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Siqi Liu: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Yanan Zhou: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Qi Gu: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Jingjing Lu: University of Chinese Academy of Sciences Beijing 100049 China
Tuo Wei: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Zeyu Gao: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Jingyi Zang: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China
Jun Wang: University of Chinese Academy of Sciences Beijing 100049 China
Moshi Song: State Key Laboratory of Organ Regeneration and Reconstruction Institute of Zoology Chinese Academy of Sciences Beijing 100101 China

DOI: https://doi.org/10.1002/advs.202417827
Journal volume & issue: Vol. 12, no. 21
pp. n/a – n/a

Abstract

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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.

Published in Advanced Science

ISSN: 2198-3844 (Online)
Publisher: Wiley
Country of publisher: Germany
LCC subjects: Science
Website: https://onlinelibrary.wiley.com/journal/21983844

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