The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through 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.
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Global research trends in bacteriophage and gut microbiota: a bibliometric and visual analysis from 2012 to 2025 Hui-Fang Kuang, Xiong-Yilang Jiang, Song-Yan Tie, Kun Lian, Mu-Yi Hao, Hang Xu, Xiao Huang, Yi Yang, Qian Guo, Jie Li, Ling-Li Chen Frontiers in Microbiology.2026;[Epub] CrossRef
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Gut microbial signatures of advanced hepatocellular carcinoma and their potential diagnostic value Yan Wang, Zhen Yang, Chuang Liu, Yufeng Liu, Zhongyuan Bai, Wentao Miao, Tiantian Zhang, Yan Wang, Xiang Li, Zhiyong Lai, Jun Xu Frontiers in Microbiology.2026;[Epub] CrossRef
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The intratumoral microbiome in colorectal cancer: origins, microenvironmental interactions, and new horizons in precision medicine Xuemei Li, Qian Wang, Qiang Yuan, Li Wang Frontiers in Immunology.2026;[Epub] CrossRef
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Microbiome and metabolite signatures for cirrhosis to HCC risk stratification: progress, controversies, and gaps Yanan Duan, Mengting Yang, Miaomiao Li, Yu Sun, Shiguo Liu Frontiers in Cellular and Infection Microbiology.2026;[Epub] CrossRef
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Harnessing the gut microbiota in extra-intestinal cancers: from causal evidence to immunotherapy strategies Elisa Mattavelli, Valentina Da Prat, Salvatore Corallo, Alice Tartara, Simone Figini, Francesca De Simeis, Sofia Marino, Anna Uggè, Riccardo Caccialanza, Paolo Pedrazzoli, Angioletta Lasagna Immunotherapy.2026; : 1. CrossRef
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Deciphering the circadian rhythm in colorectal cancer: a bibliometric analysis of research landscape and trends Linzi Chen, Zhongjie Wang, Ningkun Xiao, Jinhui Liu, Yuhan Tao, Sifang Zhang Frontiers in Oncology.2025;[Epub] CrossRef
Mechanism of activation of the Nrf2-Keap1 pathway by fermented Chinese herbal medicines via the gut-liver axis to alleviate cadmium-induced hepatotoxicity Li Jiang, Qiuhong Wu, Yilei Liang, Zhiwen Yang, Guang Fan, Pan Zhou, Xinyue Liu, Yachao Wang Environmental Chemistry and Ecotoxicology.2025; 7: 1300. CrossRef
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Tumor microenvironment and macroenvironment: A new perspective on holistic oncology Qun Chen, Kuirong Jiang, Michael S. Bronze, Min Li, Courtney W. Houchen, Yuqing Zhang Cancer Letters.2025; 634: 218076. CrossRef
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The role of hypothyroidism in cirrhosis pathogenesis: A retrospective cohort study and multi-omics integration analysis Ziyang Yang, Weixuan Liang, Qi Zhang, Can Weng, Hao Deng, Zhuofeng Wen, Jingyi Wu, Jingwen Deng, Zhixin Xie, Yiwei Lin, Xiuling Fu, Chengxin Gu, Tao Yang, Hui Yang, Jiyuan Zhou, Renato Polimanti PLOS Genetics.2025; 21(11): e1011947. CrossRef
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