Gut microbiome-brain-cirrhosis axis

Abstract

Cirrhosis is characterized by inflammation, degeneration, and fibrosis of liver tissue. Along with being the most common cause of liver failure and liver transplant, cirrhosis is a significant risk factor for several neuropsychiatric conditions. The most common of these is HE, which is characterized by cognitive and ataxic symptoms, resulting from the buildup of metabolic toxins with liver failure. However, cirrhosis patients also show a significantly increased risk for neurodegenerative diseases such as Alzheimer and Parkinson diseases, and for mood disorders such as anxiety and depression. In recent years, more attention has been played to communication between the ways the gut and liver communicate with each other and with the central nervous system, and the way these organs influence each other's function. This bidirectional communication has come to be known as the gut-liver-brain axis. The gut microbiome has emerged as a key mechanism affecting gut-liver, gut-brain, and brain-liver communication.Clinical studies and animal models have demonstrated the significant patterns of gut dysbiosis when cirrhosis is present, both with or without concomitant alcohol use disorder, and have provided compelling evidence that this dysbiosis also influences the cognitive and mood-related behaviors. In this review, we have summarized the pathophysiological and cognitive effects associated with cirrhosis, links to cirrhosis-associated disruption of the gut microbiome, and the current evidence from clinical and preclinical studies for the modulation of the gut microbiome as a treatment for cirrhosis and associated neuropsychiatric conditions.

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

“…The mitigation of neurocognitive impairments may be exerted by treatment of the primary disease (e.g., NAFLD and hepatic fibrosis) or compensatory measures of liver function (e.g., albumin infusion) ( Cheon and Song, 2022 ; Fagan et al, 2023 ). In addition, several lines of evidence have demonstrated beneficial effects on liver function and neurocognition by reestablishing intestinal flora homeostasis ( Cheon and Song, 2022 ; Smith et al, 2023 ).…”

Keratin 18‐M65: A biomarker for early‐stage alcohol‐associated liver disease

“…There is also increasing interest in modulating the microbiome as a therapeutic intervention for both AUD and ALD. Indeed, there are recent animal and human studies to support this concept using both fecal transplantation and probiotic therapy (Jiang et al, 2023; Kouno et al, 2023; Singhal et al, 2021; Smith et al, 2023; Vatsalya et al, 2023; Wolstenholme et al, 2022).…”

“…This further links the gut: liver axis in the early pathogenesis of ALD. There are multiple lines of evidence from both humans and animal models that the microbiome and microbial metabolites play a role in both drinking behavior and alcohol‐related liver injury (Jiang et al, 2023; Kouno et al, 2023; Singhal et al, 2021; Smith et al, 2023; Vatsalya et al, 2023; Wolstenholme et al, 2022). There is also increasing interest in modulating the microbiome as a therapeutic intervention for both AUD and ALD.…”

The RIVET RCT: Rifamycin SV MMX improves muscle mass, physical function, and ammonia in cirrhosis and minimal encephalopathy

“…Cirrhosis and associated cognitive impairment due to minimal hepatic encephalopathy (MHE) have major challenges with daily function and poor clinical outcomes such as the development of overt hepatic encephalopathy (OHE). 1 , 2 The pathogenesis of MHE and OHE is related to an altered gut-liver-brain axis and medications focused on gut microbiome have successfully been used in MHE. 3 There is an alteration of gut microbial composition and function (bile acid changes, endotoxemia, and gut metabolic products) in cirrhosis, which worsens with disease progression with MHE and OHE.…”