BACKGROUND:
Hepatic encephalopathy (HE) is a severe neuropsychiatric complication resulting from hepatic dysfunction, yet its precise pathophysiological mechanisms remain incompletely understood. Emerging evidence underscores the pivotal role of the gut-brain axis (GBA), a bidirectional communication system linking the gastrointestinal tract and central nervous system in mediating the onset and progression of HE.

OBJECTIVE:
This review explores the intricate interactions between gut microbiota, neuroinflammation, and hepatic dysfunction, aiming to elucidate the mechanistic pathways by which alterations in the gut-brain axis contribute to the development of hepatic encephalopathy.

METHODS:
Relevant literature examining the gut microbiome, microbial metabolites, neuroinflammatory cascades, neurotransmitter signaling, and therapeutic interventions was systematically analyzed to synthesize a comprehensive understanding of GBA-mediated HE pathogenesis.

RESULTS:
Dysbiosis of the gut microbiota in liver disease patients disrupts metabolic homeostasis and amplifies systemic and neuroinflammatory responses. Metabolites such as ammonia and short-chain fatty acids, alongside altered bile acid signaling, contribute to neuronal toxicity and impaired cognitive function. Nutritional modulation, probiotics, and fecal microbiota transplantation (FMT) have demonstrated therapeutic promise by restoring microbial balance and mitigating neurotoxic effects.

CONCLUSIONS:
The gut-brain axis represents a crucial therapeutic and diagnostic frontier in hepatic encephalopathy. Targeting microbiota-driven metabolic and inflammatory pathways offers significant potential for precision medicine approaches, enabling personalized management strategies that improve neurological outcomes in HE.