Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation
The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as <i>Anaerotruncus colihominis</i> and <i>Dysosmobacter welbionis</i>, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.
Authors
- Xue‐Fei Tian (ORCID: https://orcid.org/0000-0003-4786-0844)
- Pei Liu (ORCID: https://orcid.org/0000-0002-6854-4333)
- Ruoyu Wang (ORCID: https://orcid.org/0000-0002-3644-1284)
- Fanying Meng (ORCID: https://orcid.org/0000-0003-2496-1386)
- Zhe Deng (ORCID: https://orcid.org/0000-0002-9776-7261)
- Xiaozheng Li (ORCID: https://orcid.org/0000-0002-0802-6454)
- Jingjing Dai (ORCID: https://orcid.org/0000-0001-8337-7281)
- Lihuai Wang (ORCID: https://orcid.org/0009-0007-4635-3230)
- Si Mei (ORCID: https://orcid.org/0000-0002-4263-1121)
- Bo Zou (ORCID: https://orcid.org/0000-0001-6372-0388)
- Zhaoguang Ouyang
- Zhenyu Wang (ORCID: https://orcid.org/0000-0002-5114-435X)
- Quan Li (ORCID: https://orcid.org/0000-0001-8563-1802)
- Rongrong Wang (ORCID: https://orcid.org/0009-0004-3195-4904)
- Xue Zhang (ORCID: https://orcid.org/0000-0002-5782-2174)
- Qianqian Guo (ORCID: https://orcid.org/0000-0003-1510-6070)
- Chun Yi (ORCID: https://orcid.org/0000-0003-3506-2781)
- Xie Mingxia
- Qing Wang
- Kexin Mao
- Tianhao Deng (ORCID: https://orcid.org/0000-0001-5094-5879)
Institutions
- Hunan University of Traditional Chinese Medicine (CN)
- Hunan University (CN)
- Shenzhen University (CN)
- State Administration of Traditional Chinese Medicine of the People's Republic of China (CN)
- Integrated Chinese Medicine (China) (HK)
- Shenzhen Bay Laboratory (CN)
- First Affiliated Hospital of Hunan University of Traditional Chinese Medicine (CN)
- Hunan Academy of Traditional Chinese Medicine (CN)
- Viva Biotech (China) (CN)
- Sidney Kimmel Comprehensive Cancer Center (US)
- Tianjin Medical University (CN)
Publication Details
- Journal
- Gut Microbes
- Published
- 2025-03-18
- DOI
- https://doi.org/10.1080/19490976.2025.2476561
- Citations
- 27
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 21.76
Funders
- National Natural Science Foundation of China