Critical metabolites such as bile acids, short-chain fatty acids, lipopolysaccharide, polyamines, and trimethylamine N-oxide (TMAO) regulate HCC progression by remodeling the tumor immune microenvironment, reprogramming immunometabolism, and modulating core signaling pathways including NF-κB, STAT3, and mTOR. The gene discussed is NFKB1; the disease is hepatocellular carcinoma.