Novel Insights Into Pathogenesis and Therapeutic Strategies of Hepatic Encephalopathy, From the Gut Microbiota Perspective

Abstract

Since the 1950s, gradual changes in the gut microbiota of patients with hepatic encephalopathy have been observed. Previous research has indicated potential associations between the gut and brain, and the gut microbiota is becoming a hot topic in research on diseases of the nervous system. However, for the past few decades, studies of hepatic encephalopathy have been restricted to controlling the gut microbiota during macroscopic manipulation, such as probiotic intervention, while its clinical use remains controversial, and the cellular mechanisms underlying this condition are still poorly understood. This thesis seeks to comprehensively understand and explain the role of gut microbiota in hepatic encephalopathy as well as analyze the effects of intervention by regulating the gut microbiota. Evidence is presented that shows that dysbiosis of the gut microbiota is the primary pathological driver of hepatic encephalopathy and impacts pathologic progression via complex regulatory networks. As a result, suggestions were identified for future mechanistic research and improvements in therapeutic strategies for hepatic encephalopathy.

Ameliorative Effect of Chitosan Oligosaccharides on Hepatic Encephalopathy by Reshaping Gut Microbiota and Gut–Liver Axis

“…Ruminococcaceae is negatively associated with inflammation and Bacteroides spp. is related to the onset of systemic immune response and the prevention of bacterial translocation. , Moreover, Dorea and Roseburia can be thought to be biomarkers of inflammation and cognition that are associated with acetylcholinesterase inhibitors …”

“…It is commonly agreed that hyperammonemia is responsible for the pathological, clinical, and neurochemical changes in HE, and ammonia levels are extensively utilized for diagnosing HE patients. Increasing evidence shows that the development of HE is driven by its metabolic by-products and the change in the structure of the gut microbiota, along with a background of leaky gut and local and systemic inflammation . COS has obtained enormous attention due to nontoxic, functional, biodegradable natural, and biological activities for various applications. , Recently, the utilization of COS has demonstrated great potential in health care because it does not show any toxic influence after oral administration to rats at doses ranging from 500 to 2000 mg/kg/day for 28 days .…”

“…Microbiome manipulation seems to be a promising method of HE therapy, which leads to a favorable change in the gut microbiota. The targets for new treatment methods, such as prebiotics, can be provided by the changed interactions of the brain–gut microbiome in HE . Therefore, gut microorganisms as well as their metabolites are the essential targets for treating and preventing HE.…”

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“…The temperature required for storage of these microbiota capsules is about -80°C (112°F) for half year (6 months) before use [Figure 2]. [28] Mode of action of FMT…”

Trust your gut: The human microbiome

“…There is ongoing research into the potential use of FMT for other gastrointestinal diseases where disruption of the gut microbiome may be relevant. A recent study looking at FMT in the treatment of hepatic encephalopathy produced some encouraging results (Liu et al., 2021). There is also emerging evidence for use of FMT in Primary Scelrosing Cholangitis.…”