Microbiome-gut-liver axis in chronic inflammation and cancer immunotherapy: Multi-omics Insights and a translational roadmap toward personalized medicine.

Gut-liver axis is critical to integrate microbial, metabolic, and immune signaling networks to control hepatic homeostasis and carcinogenesis. Gut microbial balance disruption (dysbiosis) stimulates chronic inflammation, metabolic disorders, and transition from non-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). Latest evidence points to the gut and intratumoral microbiota's roles in shaping immune regulation and responsiveness to immunotherapy against cancer. This review encapsulates the latest evidence on the microbiome-gut-liver axis in chronic liver disease and cancer, highlighting multi-omics evidence, mechanisms of immune modulation, and translational avenues to microbiome-informed precision medicine in HCC. Comprehensive literature search on PubMed, Scopus, Web of Science, and Embase (until September 2025) focused on the gut-liver axis, microbiome, immune checkpoint inhibitors (ICIs), and multi-omics integration. Only mechanistically and translationally relevant peer-reviewed studies were included. Dysbiosis disrupts the permeability of the intestines and metabolism of bile acids and affects immune signaling to induce hepatic inflammation and fibrogenesis. Multi-omic studies identify key microbial metabolites, short-chain fatty acids, secondary bile acids, and tryptophan derivatives to govern the function of T-cell and responsiveness to checkpoint. Clinical research demonstrates that increased abundance of taxa like Akkermansia muciniphila, Bifidobacterium longum, and Faecalibacterium prausnitzii improves ICI efficacy but antibiotic exposure decreases therapeutic efficacy. Tumor-residing microbiomes further determine immune infiltration and risk of recurrence. Multi-omic and computational integration of gut and tumor microbiome data provides mechanistic insight to microbial-informed immunotherapy. Standardization, regulatory convergence, and ethical guidelines are critical to translate microbiome therapeutics, namely fecal microbiota transplantation, engineered probiotics, and metabolite-directed interventions to safe and individualized strategies to treat liver cancer.