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

Daniela Campion, Ilaria Giovo, Paola Ponzo, Giorgio M Saracco, Federico Balzola, Carlo Alessandria, Daniela Campion, Ilaria Giovo, Paola Ponzo, Giorgio M Saracco, Federico Balzola, Carlo Alessandria

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

Conflict of interest statement

Conflict-of-interest statement:Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

Figures

Figure 1
Figure 1
Multifactorial pathogenesis of hepatic encephalopathy. The figure summarizes the pathogenetic mechanisms at all levels of the gut-liver-brain axis underlying the development of hepatic encephalopathy. In this context, the interplay between systemic inflammation and hyperammonemia plays a central role (see text for details). CNS: Central nervous system; GABA: Gamma-aminobutyric acid; GI: Gastrointestinal; IL: Interleukin; NH4: Ammonia; NO: Nitric oxide; PAMPs: Pathogen associated molecular patterns; ROS: Reactive oxygen species; SIBO: Small intestine bacterial overgrowth; SIRS: Systemic inflammatory response syndrome; TNF-α: Tumor necrosis factor-alpha.
Figure 2
Figure 2
Leaky gut in liver cirrhosis. Multiple factors are involved in the increase of intestinal permeability found in cirrhotic patients. SCFA: Short-chain fatty acids.
Figure 3
Figure 3
Potential benefits of dietary modulation in hepatic encephalopathy. AAA: Aromatic amino acids; BCAA: Branched-chain amino acids; CNS: Central nervous system; LOLA: L-ornithine–L-aspartate; SCFA: Short-chain fatty acids.

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