Gut–Liver Axis and Microbiome-Based Hepatoprotective Strategies: Emerging Therapeutic Approaches for Liver Diseases

The gut–liver axis is a complex bidirectional communication network that plays an essential role in maintaining hepatic and intestinal homeostasis. The gut microbiota, intestinal barrier, portal circulation, bile acids, microbial metabolites, and immune signaling collectively regulate hepatic metabolism, inflammation, and immune responses. Alterations in gut microbial composition and function, commonly referred to as dysbiosis, can impair intestinal barrier integrity, increase microbial translocation and endotoxemia, alter bile acid metabolism, and promote oxidative stress and inflammatory signaling, thereby contributing to the development and progression of various liver diseases. This review discusses the structural and functional components of the gut–liver axis and summarizes the mechanisms linking gut dysbiosis with liver injury, including intestinal permeability, lipopolysaccharide-mediated inflammation, oxidative stress, and immune dysregulation. The role of gut microbiota in drug-induced liver injury, alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease, steatohepatitis, viral hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma is also highlighted. Particular emphasis is placed on microbiome-derived molecules, including short-chain fatty acids, bile acids, indole derivatives, tryptophan metabolites, bacteriocins, and extracellular vesicles, as potential hepatoprotective mediators. Furthermore, emerging microbiome-based strategies such as probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, precision nutrition, dietary polyphenols, herbal medicines, and nanotechnology-based targeted delivery systems are discussed. Despite promising evidence, challenges related to microbiome variability, disease-specific dysbiosis, safety, standardization, and limited clinical validation remain. Future advances in personalized microbiome therapy, engineered probiotics, microbiome-derived therapeutics, artificial intelligence, and gut–liver organoid models may facilitate the development of precise and effective hepatoprotective interventions.