The gut-liver axis in chronic liver diseases: An integrative immunopathological perspective bridging animal models and human evidence.

Chronic liver diseases (CLDs) represent a major global health burden, affecting over 1.5 billion individuals and causing approximately two million deaths annually. Their prevalence is escalating worldwide, largely driven by the growing incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), viral hepatitis, and alcohol-related liver injury. This trend is further exacerbated by modern dietary habits, sedentary lifestyles, and increasing rates of obesity and metabolic syndrome. Despite advances in diagnosis and treatment, effective therapeutic options remain limited, underscoring the urgent need to elucidate the underlying mechanisms driving liver injury and progression. The gut-liver axis displays a crucial function in preserving metabolic equilibrium and immune homeostasis. Interruption of this bidirectional communication is progressively identified as a main cause of the initiation and development of CLDs. This literature comprehensively inspects the immunopathological mechanisms linking the liver and gut, integrating confirmation from both human studies and animal models to identify clinically relevant targets. We explore current findings on gastrointestinal microbial populations, gastrointestinal barrier pathway, hepatic immune activities, and emerging therapeutic interventions. Particular attention is given to how microbial metabolites, immune cell activation, and bile acid signaling pathways collectively influence liver inflammation and fibrosis. While preclinical models provide valuable mechanistic insights, human studies reveal complex and heterogeneous immune responses. Novel strategies aimed at modulating the microbiota, enhancing barrier integrity, and regulating immune signaling show promising translational potential. Given the accelerating global burden of CLDs, a deeper understanding of the gut-liver immune interface is now more critical than ever for developing precision-based diagnostics and targeted interventions that can effectively halt or reverse disease progression.