Integrative omics perspectives on the gut-liver axis in chronic liver diseases: mechanisms and therapeutic potential

Chronic liver diseases, including chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease (MASLD), autoimmune liver diseases (AILD), liver fibrosis and cirrhosis, and hepatocellular carcinoma (HCC), are rising in prevalence and weigh heavily on public health worldwide. The rapid development and integration of multi-omics technologies-including microbiome, transcriptomics, proteomics, and metabolomics-have moved the understanding of chronic liver disease pathogenesis and progression into a new phase. The “gut-liver axis”-a bidirectional communication network linking the gut microbiota to the liver through immune, metabolic, and neuroendocrine pathways-is now understood to shape the onset, progression, and outcomes of chronic liver diseases. It governs gastrointestinal health and disease and is a key mediator of host-environment interactions. This review aims to compare gut-liver axis mechanisms across chronic liver diseases from an integrative omics perspective, focusing on their similarities and differences. It examines microbial composition and functional alterations, intestinal barrier integrity, microbial metabolites (such as nutrients, microbial antigens, short-chain fatty acids, and bile acids), and immune crosstalk in disease evolution. It also assesses the evidence and clinical translational potential of gut-liver axis–targeted interventions, including probiotics, fecal microbiota transplantation, dietary interventions, and targeted therapies. Synthesizing integrative multi-omics work on the gut-liver axis can provide a systematic reference for mechanistic insight, early warning, and precision prevention and treatment of chronic liver diseases. It can also offer a scientific basis for public-health strategies to control liver disease.