| Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer |
| Chenyang Li1,2,3, Chujun Cai5,6, Chendong Wang1,2,3, Xiaoping Chen1,2,3,4, Bixiang Zhang1,2,3,4, Zhao Huang1,2,3 |
1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
2Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, Hubei, China
3Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
4Key Laboratory of Organ Transplantation, Ministry of Education, Chinese Academy of Medical Sciences; NHC Key Laboratory of Organ Transplantation, Wuhan, Hubei, China
5Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
6Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China |
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Received: September 30, 2024 Revised: November 22, 2024 Accepted: December 6, 2024
*Chenyang Li, Chujun Cai and Chendong Wang contributed equally to this work. |
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| ABSTRACT |
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The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver though a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy. |
| KeyWords:
Gut microbiota; Gut-liver axis; Liver cancer; Intratumoral microbiota; Immune regulation; Metabolic modulation; Clinical translation |
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