The Gut‒Liver Axis in Liver Disease: Molecular Mechanisms and Therapeutic Targets

ABSTRACT The increasing global burden of liver disease is a growing public health challenge. The gut‒liver axis, a bidirectional communication system between the intestine and liver via the portal circulation and biliary tract, is crucial for maintaining metabolic and immune homeostasis. Dysregulation of the gut‒liver axis has been recognized as a key driver of the pathogenesis of various liver diseases. However, its complex molecular mechanisms and the resulting precision therapeutic strategies remain under investigation. This review elaborates on the core components of the gut‒liver axis and the key mechanisms of gut‒liver axis imbalance in metabolic dysfunction‐associated fatty liver disease, alcohol‐associated liver disease, cirrhosis, spontaneous bacterial peritonitis, and primary liver cancer. We discuss the core roles of intestinal barrier dysfunction, dysbiosis, liver immune activation, and bacterial metabolite imbalance. Furthermore, we systematically review emerging therapeutic strategies targeting this axis, such as restoring barrier function, correcting dysbiosis, regulating bacterial metabolism, and blocking deleterious signaling. This review provides an integrative perspective on the pathophysiology of liver diseases and highlights the great potential of targeting the gut‒liver axis in translational medicine to improve the treatment paradigm for liver diseases.