Rethinking hepatic encephalopathy: Gut microbes, neurotoxins and the therapeutic horizon

Abstract

Section snippets

Background and context

Hepatic encephalopathy (HE) is a severe complication of liver disease, indicating progression in decompensated cirrhosis and acute liver failure, and is associated with an increased risk of mortality.[1], [2], [3] The pathogenesis of HE is primarily driven by hyperammonemia, which acts as a neurotoxin, leading to astrocyte swelling and cerebral edema, thus contributing to disease progression. Additionally, systemic inflammation, often triggered by gut-derived endotoxins, plays a significant

Objectives, methods and findings

To explore the mechanisms of brain dysfunction in liver disease, He X et al. investigated the gut-brain axis by analyzing metagenomic data from the gut from four cohorts of patients with cirrhosis. They identified gut-brain modules associated with HE, with the monoamine synthesis pathway showing the strongest correlation. This pathway, catalyzed by aromatic L-amino acid decarboxylases was predominantly found in Ruminococcus gnavus (R. gnavus). Further analysis uncovered novel genes in the

Significance of findings

He et al. demonstrated that R. gnavus in the gut can produce PEA, a neuroactive molecule that accumulates in the brain due to impaired hepatic clearance in liver disease. However, the exact role of R. gnavus in this process remains unclear. It is uncertain whether the involvement of R. gnavus is a direct, quantitative result of cirrhosis-related dysbiosis – where its abundance increases in the gut – or if it is a species-specific alteration in PDC expression as a response to changing

Financial support

The author did not receive any financial support to produce this manuscript.

Conflict of interest

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