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

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.

• Authors: Hui Lin, Liping Meng, Zhenzhu Sun, Shiming Sun, Xingxiao Huang, Na Lin, Jie Zhang, Wenqiang Lu, Qi Yang, Jufang Chi, Hangyuan Guo
• Journal: Circulation. Heart failure (Circ Heart Fail) Vol. 14 Issue 10 Pg. e008220 (10 2021) ISSN: 1941-3297 [Electronic] United States
• PMID: 34665676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Doxorubicin

Topics

• Animals
• Apoptosis (drug effects)
• Cardiotoxicity (drug therapy, metabolism)
• Doxorubicin (pharmacology)
• Gastrointestinal Microbiome (drug effects, genetics)
• Heart (drug effects)
• Heart Failure (drug therapy, metabolism)
• Male
• Mitochondria (drug effects)
• Myocardium (metabolism)
• Rats, Sprague-Dawley
• Wine (adverse effects)
• Rats