The intestinal microbiome, often characterized as humanity’s “secondary genome,” possesses a genetic repertoire that dwarfs the coding capacity of the human genome by orders of magnitude. The essential architecture of this system is constituted by a vast phylogenetic tapestry of luminal microorganisms, whose dynamic symbiosis serves as a critical determinant of intestinal mucosal homeostasis and functional fidelity. The past decade has witnessed a paradigm shift in biomedical sciences, wherein technological breakthroughs in microbial single-cell genomics and spatial metatranscriptomics have unveiled the gut ecosystem’s pivotal role in host physiology. Emerging evidence from gut-liver interface research demonstrates how microbial-derived signals, facilitated by the portal circulatory nexus, mechanistically contribute to the initiation and perpetuation of chronic hepatopathies. This review elucidates the pathophysiological mechanisms through which intestinal dysbiosis propagates chronic hepatopathies, with the ultimate objective of informing novel diagnostic paradigms and therapeutic interventions.