Abstract
Hepatic encephalopathy (HE) is a severe complication of advanced liver disease and acute liver failure. The clinical spectrum ranges from minor cognitive dysfunctions to lethargy, depressed consciousness, and coma and significantly impact the quality of life, morbidity, and mortality of the patients. It is commonly accepted that the gut milieu is essential for the development of HE; however, despite intensive research efforts, the pathogenesis of HE is still not fully elucidated. As our knowledge of gut microbiota moves from the pioneering era of culture-dependent studies, the connection between microbes, inflammation, and metabolic pathways in the pathogenesis of HE is becoming increasingly clear, providing exciting therapeutic perspectives. This review will critically examine the latest research findings on the role of gut microbes in the pathophysiological pathways underlying HE. Moreover, currently available therapeutic options and novel treatment strategies are discussed.
Highlights
Hepatic encephalopathy (HE) encompasses a broad spectrum of neurological or psychiatric abnormalities ranging from minor cognitive dysfunction to lethargy, depressed consciousness, and coma occurring in patients with liver insufficiency or portosystemic shunting (Vilstrup et al, 2014)
In a randomised, placebo-controlled trial involving 55 patients with minimal HE (MHE), Liu et al demonstrated that a symbiotic treatment with probiotics and fermentable fiber effectively increased the fecal content of Lactobacillus spp. at the expense of the overgrowth of pathogenic bacteria, such as Escherichia coli and Staphylococcus spp
Symbiotic treatment was further associated with reduction of serum ammonia and reversal of MHE in 50% of the patients compared to the placebo group (Liu et al, 2004)
Summary
Hepatic encephalopathy (HE) encompasses a broad spectrum of neurological or psychiatric abnormalities ranging from minor cognitive dysfunction to lethargy, depressed consciousness, and coma occurring in patients with liver insufficiency or portosystemic shunting (Vilstrup et al, 2014). It is commonly accepted that neurological impairment and cognitive decline provoked by liver dysfunction result from blood-derived factors influencing the permeability and altering the integrity of the blood-brain barrier. The concomitant decrease in bile acids (BAs) synthesis due to liver failure synergistically act with SIBO to determine pathological changes in the intestinal microbiota composition, mainly characterised by a massive reduction in microbial diversity, a decline in autochthonous non-pathogenic bacteria (Bacteroidetes, Ruminococcus, Roseburia, Veillonellaceae, and Lachnospiraceae) and an overgrowth of potentially pathogenic species (Fusobacteria, Proteobacteria, Enterococcaceae, and Streptococcaceae) (Fukui, 2015; Acharya and Bajaj, 2017). The impaired intestinal barrier integrity enhances bacterial translocation and the release of bacterial endotoxins in circulation, such as lipopolysaccharides, flagellin, peptidoglycan, and microbial nucleic acids, perpetuating liver damage and contributing to systemic inflammation responsible for blood-brain barrier dysfunction and neuroinflammation (Shawcross et al, 2004; Shawcross et al, 2007; Shawcross et al, 2011; Dhiman, 2012).
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