Yellow Wine Polyphenolic Compound Protects Against Doxorubicin-Induced Cardiotoxicity by Modulating the Composition and Metabolic Function of the Gut Microbiota

  • Circ Heart Fail. 2021 Oct;14(10):e008220. doi: 10.1161/CIRCHEARTFAILURE.120.008220.
Hui Lin   #  1 ,  Liping Meng   #  1 ,  Zhenzhu Sun   #  2 ,  Shiming Sun  3 ,  Xingxiao Huang  4 ,  Na Lin  5 ,  Jie Zhang  1 ,  Wenqiang Lu  4 ,  Qi Yang  5 ,  Jufang Chi  1 ,  Hangyuan Guo  6
Affiliations
  • 1. Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, China (H.L., L.M., J.Z., J.C.).
  • 2. Department of Cardiology, Taizhou Hospital of Zhejiang Provence, China (Z.S.).
  • 3. The First Clinical Medical College, Wenzhou Medical University, Zhejiang, China (S.S.).
  • 4. Zhejiang University School of Medicine, Hangzhou, China (X.H., W.L.).
  • 5. Zhejiang Chinese Medical University, Hangzhou, China (N.L., Q.Y.).
  • 6. College of Medicine, Shaoxing University, Zhejiang, China (H.G.).
  • # Contributed equally.
PMID: 34665676 DOI: 10.1161/CIRCHEARTFAILURE.120.008220
Abstract

Background: Dietary Polyphenols help to prevent cardiovascular diseases, and interactions between Polyphenols and gut microbiota are known to exist. In this study, we speculated that gut microbiota-mediated metabolite regulation might contribute to the anticardiotoxic effects of yellow wine polyphenolic compound (YWPC) in doxorubicin (DOX)-treated rats.

Methods: 16S-rDNA Sequencing was performed to analyze the effects of YWPC on the gut microbiota in DOX-treated rats (n=6). Antibiotics were used to investigate the contribution of the altered microbiome to the role of YWPC (n=6). Plasma metabolomics were also analyzed by untargeted gas chromatography-mass spectrometry systems.

Results: YWPC ameliorated DOX-mediated cardiotoxicity, as evidenced by increased cardiac and mitochondrial function and reduced levels of inflammation and myocardial Apoptosis (P<0.05 for all). The low abundance of Escherichia-Shigella, Dubosiella, and Allobaculum, along with enrichment of Muribaculaceae_unclassified, Ralstonia, and Rikenellaceae_RC9_gut_group in the gut, suggested that YWPC ameliorated DOX-induced microbial dysbiosis. YWPC also influenced the levels of metabolites altered by DOX, resulting in lower arachidonic acid and linoleic acid metabolism and higher tryptophan metabolite levels (P<0.05 for all). Correlational studies indicated that YWPC alleviated DOX-induced inflammation and mitochondrial dysfunction by modulating the gut microbial community and its associated metabolites. Antibiotic treatment exacerbated cardiotoxicity in DOX-treated rats, and its effect on the gut microbiota partly abolished the anticardiotoxic effects of YWPC, suggesting that the microbiota is required for the cardioprotective role of YWPC.

Conclusions: YWPC protected against DOX-induced cardiotoxicity in a gut microbiota-dependent manner. This supports the use of dietary Polyphenols as a therapeutic approach for the treatment of cardiovascular diseases via microbiota regulation.

Keywords
cardiotoxicity; doxorubicin; gastrointestinal microbiome; metabolomics; polyphenols.
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