The Gut-Liver Axis in Cancer: Deciphering the Microbiome's Role in Hepatocarcinogenesis and Liver Metastasis

The gut-liver axis, a bidirectional communication network linking the intestinal microbiota to hepatic physiology, has emerged as a critical regulator of liver pathology, including hepatocarcinogenesis and the establishment of liver metastases. This comprehensive review delineates the mechanisms by which gut-derived microbial signals, including live bacteria, bacterial metabolites, and pathogen-associated molecular patterns (PAMPs), traverse a compromised intestinal barrier to directly influence the hepatic microenvironment. We detail how these factors drive chronic inflammation, fibrosis, and metabolic dysfunction, thereby creating a permissive niche for the development of primary hepatocellular carcinoma (HCC). Furthermore, we examine how gut dysbiosis systemically reprograms the liver into a receptive soil for metastatic seeding and outgrowth from extrahepatic malignancies, such as colorectal, pancreatic, and breast cancers. Our synthesis of preclinical models and clinical cohort studies highlights specific microbial signatures and metabolites (e.g., lipopolysaccharide, deoxycholic acid, and butyrate) with prognostic value. Finally, we evaluate emerging microbiome-targeted therapeutic strategies, including fecal microbiota transplantation (FMT), precision probiotics, and bile acid modulators, as novel adjuvants to enhance the efficacy of existing oncologic therapies for liver cancers. We conclude that targeting the gut-liver axis represents a paradigm-shifting approach for the prevention and treatment of both primary and metastatic liver malignancies, urging integrated multi-omics research and dedicated clinical trials to realize its full translational potential.

کلیدواژه ها:

Gut-Liver Axis ، Hepatocellular Carcinoma ، Liver Metastasis ، Dysbiosis ، Microbial Translocation ، Fecal Microbiota Transplantation