Lin Hui, Shao Xian, Gu Haodi, Yu Xinrou, He Lingyan, Zhou Jiedong, Zhong Zuoquan, Guo Shitian, Li Dan, Chen Fei, Song Yongfei, Xu Lili, Wang Ping, Meng Liping, Chi Jufang, Lian Jiangfang
Department of Cardiology, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
Medical Research Center, Shaoxing People's Hospital, Shaoxing, China.
NPJ Biofilms Microbiomes. 2025 May 23;11(1):86. doi: 10.1038/s41522-025-00712-y.
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.
多柔比星（DOX）是一种关键的化疗药物，但也是多柔比星诱导的心脏毒性（DIC）的主要原因，限制了其临床应用。嗜黏蛋白阿克曼氏菌（A. muciniphila）作为一种益生菌在治疗代谢综合征方面具有益处，但其在DIC背景下的作用尚不确定。在这里，对蒽环类药物治疗患者和DIC小鼠粪便样本进行的16S rRNA测序显示，嗜黏蛋白阿克曼氏菌明显减少。在体外实验的支持下，心脏转录组学研究表明，在正常和抗生素处理的C57BL/6小鼠中，嗜黏蛋白阿克曼氏菌定殖可通过激活PPARα/PGC1α信号通路改善线粒体功能并减轻DIC。进一步分析发现，给予嗜黏蛋白阿克曼氏菌后，微生物组-代谢组网络发生了重组，这有助于保护心脏免受DIC侵害。值得注意的是，补充嗜黏蛋白阿克曼氏菌可提高色氨酸代谢物吲哚-3-丙酸（IPA）的血清水平，IPA与心脏芳烃受体（AhR）结合，从而激活PPARα/PGC1α信号通路。总之，我们的研究揭示了嗜黏蛋白阿克曼氏菌作为益生菌减轻DIC的潜力。
