2. Academic Validation
  3. Akkermansia muciniphila ameliorates doxorubicin-induced cardiotoxicity by regulating PPARα-dependent mitochondrial biogenesis

Akkermansia muciniphila ameliorates doxorubicin-induced cardiotoxicity by regulating PPARα-dependent mitochondrial biogenesis

  • NPJ Biofilms Microbiomes. 2025 May 23;11(1):86. doi: 10.1038/s41522-025-00712-y.
Hui Lin # 1,  Xian Shao # 2,  Haodi Gu 3,  Xinrou Yu 4,  Lingyan He 5,  Jiedong Zhou 6,  Zuoquan Zhong 7,  Shitian Guo 8,  Dan Li 9,  Fei Chen 10,  Yongfei Song 1,  Lili Xu 2,  Ping Wang 11,  Liping Meng 12,  Jufang Chi 13,  Jiangfang Lian 14
Affiliations

Affiliations

  • 1 Department of Cardiology, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
  • 2 Medical Research Center, Shaoxing People's Hospital, Shaoxing, China.
  • 3 College of Medicine, Shaoxing University, Shaoxing, China.
  • 4 Department of Cardiology, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing, China.
  • 5 Department of Traditional Chinese Medicine, Shaoxing People's Hospital, Zhejiang University Shaoxing Hospital, Shaoxing, China.
  • 6 Cardiac Arrhythmia Center, The First Affiliated Hospital of Ningbo University, Ningbo, China.
  • 7 Department of Respiratory Medicine, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China.
  • 8 Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 9 Department of Haematology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China.
  • 10 Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China.
  • 11 Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China.
  • 12 Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China. Mengliping@zju.edu.cn.
  • 13 Department of Cardiology, Zhuji Affiliated Hospital of Wenzhou Medical University, Shaoxing, China. jf_chi@163.com.
  • 14 Department of Cardiology, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China. hjmpin@163.com.
  • # Contributed equally.
PMID: 40410194 DOI: 10.1038/s41522-025-00712-y
Abstract

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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