Prophylactic supplementation with Bifidobacterium infantis or its metabolite inosine attenuates cardiac ischemia/reperfusion injury

Author:

Zhang Hao12,Wang Jiawan13,Shen Jianghua124,Chen Siqi124,Yuan Hailong145,Zhang Xuan26,Liu Xu124,Yu Ying26,Li Xinran124ORCID,Gao Zeyu147,Wang Yaohui5,Wang Jun26,Song Moshi1247ORCID

Affiliation:

1. Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology Institute of Zoology, Chinese Academy of Sciences Beijing China

2. University of Chinese Academy of Sciences Beijing China

3. Department of Anesthesiology Beijing Chao‐Yang Hospital Beijing China

4. Beijing Institute for Stem Cell and Regenerative Medicine Beijing China

5. Joint National Laboratory for Antibody Drug Engineering Henan University Kaifeng China

6. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology Chinese Academy of Sciences Beijing China

7. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences Beijing China

Abstract

AbstractEmerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia–reperfusion (I/R) injury, we found that the prophylactic administration of a well‐known probiotic, Bifidobacterium infantis (B. infantis), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R‐induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro‐inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen‐glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R‐induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury.

Publisher

Wiley

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