嗜muciniphila通过调节ppar α依赖的线粒体生物发生改善阿霉素诱导的心脏毒性。

IF 9.2 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Hui Lin, Xian Shao, Haodi Gu, Xinrou Yu, Lingyan He, Jiedong Zhou, Zuoquan Zhong, Shitian Guo, Dan Li, Fei Chen, Yongfei Song, Lili Xu, Ping Wang, Liping Meng, Jufang Chi, Jiangfang Lian
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引用次数: 0

摘要

多柔比星(DOX)是一种关键的化疗药物,但也是DOX诱导的心脏毒性(DIC)的主要原因,限制了其临床应用。Akkermansia muciniphila (a . muciniphila)以其作为益生菌治疗代谢综合征的益处而闻名,但在DIC背景下的作用尚不确定。在这里,对蒽环类药物治疗的患者和DIC小鼠的粪便样本进行16S rRNA测序,发现嗜粘杆菌明显减少。体外实验支持的心脏转录组学结果显示,在正常和抗生素治疗的C57BL/6小鼠中,嗜粘杆菌定殖可通过激活PPARα/PGC1α信号通路改善线粒体功能,减轻DIC。进一步的分析发现,在a . muciniphila给药后,重组的微生物组-代谢组网络有助于DIC保护。值得注意的是,A. muciniphila的补充增加了血清中色氨酸代谢物吲哚-3-丙酸(IPA)的水平,IPA与心脏芳烃受体(AhR)结合,导致PPARα/PGC1α信号通路的激活。总之,我们的研究揭示了嗜粘杆菌作为一种益生菌在缓解DIC中的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Akkermansia muciniphila ameliorates doxorubicin-induced cardiotoxicity by regulating PPARα-dependent mitochondrial biogenesis.

Doxorubicin (DOX) is a key chemotherapeutic agent but is also a leading cause of DOX-induced cardiotoxicity (DIC), limiting its clinical use. Akkermansia muciniphila (A. muciniphila), known for its benefits as a probiotic in treating metabolic syndrome, has uncertain effects in the context of DIC. Here, 16S rRNA sequencing of fecal samples from anthracycline-treated patients and DIC mice revealed marked depletion of A. muciniphila. Cardiac transcriptomics, supported by in vitro experiments, showed that A. muciniphila colonization improved mitochondrial function and alleviated DIC by activating the PPARα/PGC1α signaling pathway in both normal and antibiotic-treated C57BL/6 mice. Further analysis uncovered a restructured microbiome-metabolome network following A. muciniphila administration, which contributed to DIC protection. Notably, A. muciniphila supplementation increased serum levels of the tryptophan metabolite indole-3-propionic acid (IPA), which binds to the cardiac aryl hydrocarbon receptor (AhR), leading to the activation of the PPARα/PGC1α signaling pathway. In conclusion, our study sheds light on the potential of A. muciniphila as a probiotic in mitigating DIC.

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来源期刊
npj Biofilms and Microbiomes
npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology
CiteScore
12.10
自引率
3.30%
发文量
91
审稿时长
9 weeks
期刊介绍: npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.
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