The Role and Mechanisms of Gut Microbiota in the Progression of Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a severe complication of end-stage liver disease that is associated with high mortality; however, its therapeutic options remain limited. The traditional mechanistic understanding focuses on ammonia neurotoxicity, although intestinal bacteria also play a significant role through the gut-liver-brain axis. This review primarily discusses the characteristics of gut dysbiosis in HE, which is marked by a progressive loss of beneficial commensals (e.g., Lachnospiraceae, Ruminococcaceae, and Faecalibacterium) and an overgrowth of potentially pathogenic bacteria (e.g., Enterobacteriaceae, Streptococcaceae, and Veillonellaceae). Unlike previous reviews which have largely focused on phylum- or genus-level changes, this review provides a species-level synthesis of gut microbial alterations in HE. We further summarise the multifaceted mechanisms by which the gut microbiota contributes to HE pathogenesis, including the impairment of intestinal barrier integrity, activation of systemic and neuroinflammation, alterations in microbial metabolites (such as ammonia, short-chain fatty acids, bile acids, and aromatic amino acids), and disruption of neuroendocrine signalling pathways. Furthermore, herein we summarise the microbiota-targeted intervention measures for HE, including aetiological treatments, drug therapies (lactulose and rifaximin), live microbial therapies (probiotics, prebiotics, synbiotics, faecal microbiota transplantation, etc.), and dietary adjustments. Emerging approaches, such as engineered bacteria and phage therapy, are also discussed, along with the barriers to their clinical translation and safety considerations. In summary, targeting the gut microbiota offers a new approach for the precise treatment of HE, although challenges remain in translating these findings into routine clinical practice.