The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Abstract

Hepatic encephalopathy (HE) is a neurological disorder that occurs in patients with liver insufficiency. However, its pathogenesis has not been fully elucidated. Pharmacotherapy is the main therapeutic option for HE. It targets the pathogenesis of HE by reducing ammonia levels, improving neurotransmitter signal transduction, and modulating intestinal microbiota. Compared to healthy individuals, the intestinal microbiota of patients with liver disease is significantly different and is associated with the occurrence of HE. Moreover, intestinal microbiota is closely associated with multiple links in the pathogenesis of HE, including the theory of ammonia intoxication, bile acid circulation, GABA-ergic tone hypothesis, and neuroinflammation, which contribute to cognitive and motor disorders in patients. Restoring the homeostasis of intestinal bacteria or providing specific probiotics has significant effects on neurological disorders in HE. Therefore, this review aims at elucidating the potential microbial mechanisms and metabolic effects in the progression of HE through the gut–brain axis and its potential role as a therapeutic target in HE.

Dose-Dependent Relationship between Protection of Thioacetamide-Induced Acute Liver Injury and Hyperammonemia and Concentration of Lactobacillus salivarius Li01 in Mice

“…However, in accordance with the research findings of Yang et al, as well as the hypothesis of ammonia intoxication ( 2 ), lower intestinal ammonia production and lower blood ammonia levels should have yielded a better prognosis. The lower the amount of ammonia that passes through the blood-brain barrier, the lower the probability of brain inflammation and brain edema, and consequently the lower the mortality rates.…”

“…Recently, combined with progressive research into gut microbiota, the function of the gut-liver axis and gut-brain axis has started to play an important role in many different diseases ( 1 , 2 ). In addition, the number of studies and clinical practices involving modulating the gut microbiota is increasing in an attempt to prevent, ameliorate, or discover a cure for some diseases.…”

The neurogliovascular unit in hepatic encephalopathy

“…Recent evidence equally shows that HE is not merely a disease of liver and brain, but rather a multiorgan dysfunction. For example, gut microbiota composition and gut barrier permeability are altered in HE, allowing for higher production and influx of ammonia and inflammatory mediators into the body (10). The muscle is an important buffer for excess ammonia.…”

“…For example, gut microbiota composition and gut barrier permeability are altered in HE, allowing for higher production and influx of ammonia and inflammatory mediators into the body. 10 The muscle is an important buffer for excess ammonia. Muscle mass loss, a hallmark of cirrhosis, additionally leads to elevated systemic ammonia concentrations and is associated with cognitive decline.…”

The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats

“…The gastrointestinal tract harbors a large number of bacteria. It is now well known that this "microbial organ" is known to modulate a variety of pathophysiological functions, including the regulation of energy storage, lipid and choline metabolism, endogenous ethanol production, immune balance, and inflammation (Vijay-Kumar et al, 2010;Mehal, 2013;Rowland et al, 2018;Chen et al, 2020;Jensen et al, 2021;Menni et al, 2021;Stacy et al, 2021). A recent study has shown that a gut microbiota-driven activation of intrahepatic B cells leads to hepatic inflammation and fibrosis during the progression of NASH (Barrow et al, 2021).…”