The Gut-Liver Axis: Molecular Mechanisms and Therapeutic Targeting in Liver Disease

The gut microbiota, often termed the "second genome", demonstrates profound therapeutic potential through its intricate biological network connecting multiple distal organs. Although microbial diversity is strongly correlated with intestinal health, its systemic implications on overall physiological homeostasis remain incompletely understood. This review synthesizes the latest evidence from clinical trials, randomized controlled trials (RCTs), systematic reviews, and meta-analyses to elucidate the biological pathways and therapeutic applications of the gut-liver axis. Through comprehensive schematic illustrations, we delineate the molecular mechanisms underlying bidirectional gut-liver communication, including microbial metabolite signaling, immune modulation networks, and enterohepatic circulation dynamics. Although interventional studies have confirmed the beneficial physiological effects of microbial modulation, current mechanistic insights are predominantly derived from animal models with limited clinical translation. While large-scale cohort studies with long-term follow-up data remain imperative, the existing evidence strongly supports the clinical value of microbiome-targeted strategies for treating hepatic diseases and related complications. These findings establish a critical theoretical framework for the development of next-generation microbial therapeutics targeting the gut-liver axis. The novelty of this review lies in its systematic classification of gut microbiota and their metabolites in the pathogenesis and treatment of various liver diseases, its detailed elaboration on signaling pathways, and its dedicated focus on the role of Traditional Chinese Medicine (TCM) in modulating the gut-liver axis.