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.

中文翻译：

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黄酒多酚化合物通过调节肠道微生物群的组成和代谢功能来防止阿霉素引起的心脏毒性


背景：膳食多酚有助于预防心血管疾病，并且已知多酚与肠道微生物群之间存在相互作用。在本研究中，我们推测肠道微生物介导的代谢调节可能有助于黄酒多酚化合物（YWPC）对阿霉素（DOX）治疗大鼠的抗心脏毒性作用。方法：通过16S-rDNA测序分析YWPC的作用对 DOX 治疗大鼠肠道微生物群的影响 (n=6)。使用抗生素来研究改变的微生物组对 YWPC 作用的贡献 (n=6)。还通过非靶向气相色谱-质谱系统对血浆代谢组学进行了分析。 结果：YWPC 改善了 DOX 介导的心脏毒性，心脏和线粒体功能增强，炎症和心肌细胞凋亡水平降低（ P <0 id=28>大肠杆菌 –志贺氏菌） 、 Dubosiella和Allobaculum ，以及肠道中Muribaculaceae_unclassified 、 Ralstonia和Rikenellaceae_RC9_gut_group的富集表明，YWPC 改善了 DOX 诱导的微生物失调，YWPC 还影响了 DOX 改变的代谢物水平，从而降低了花生四烯酸和亚油酸代谢。和更高的色氨酸代谢水平（所有相关研究P <0.05）表明，YWPC 通过调节肠道微生物群落及其相关代谢物减轻了 DOX 诱导的炎症和线粒体功能障碍。 抗生素治疗加剧了 DOX 治疗大鼠的心脏毒性，其对肠道微生物群的影响部分消除了 YWPC 的抗心脏毒性作用，表明微生物群是 YWPC 心脏保护作用所必需的。结论：YWPC 可以预防 DOX 诱导的肠道心脏毒性微生物群依赖的方式。这支持使用膳食多酚作为通过微生物群调节来治疗心血管疾病的治疗方法。