Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis

Abstract

Hepatic encephalopathy (HE) is a common and serious neuropsychiatric complication of cirrhosis, acute liver failure, and porto-systemic shunting. HE largely contributes to the morbidity of patients with liver disease, severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis. Its presentation is largely variable, manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma. The pathogenesis of HE is complex and has historically been linked with hyperammonemia. However, in the last years, it has become evident that the interplay of multiple actors, such as intestinal dysbiosis, gut hyperpermeability, and neuroinflammation, is of crucial importance in its genesis. Therefore, HE can be considered a result of a dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by “gut-centric” therapies, such as non-absorbable disaccharides, non-absorbable antibiotics, probiotics, prebiotics, and fecal microbiota transplantation. In this context dietary modifications, by modulating the intestinal milieu, can also provide significant benefit to cirrhotic patients with HE. This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis. Furthermore, it will explore the currently available therapies and the most promising future treatments for the management of patients with HE, with a special focus on the dietary approach.

Keywords: Cirrhosis; Hepatic encephalopathy; Diet therapy; Gut microbiota; Leaky gut; Hyperammonemia; Prebiotics; Probiotics; Gluten-casein free diet; Gut microbiota transplantation

Core tip: Hepatic encephalopathy (HE) is a serious complication of cirrhosis resulting from a multifactorial impairment of gut-liver-brain axis functioning. Multiple interrelated factors (e.g., intestinal hyperpermeability, dysbiosis, hyperammonemia, inflammation) cooperate in its development. “Gut-centric” therapies, including non-absorbable disaccharides, antibiotics, prebiotics, probiotics, and fecal microbiota transplantation have been successfully employed to manage HE: pertinent current knowledge will be reviewed. Furthermore, the utility of dietary modifications in this context is increasingly recognized, thus opening a new promising research path. This review sheds light on dietary therapeutic strategies for HE, exploring how they can target the mechanisms underlying gut-liver-brain axis dysregulation.