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.

Figure 1:

Multiple factors that influence the gut-brain axis in cirrhosis and resultant impact on patients, caregivers, and the healthcare system.

Figure 1:

Multiple factors that influence the gut-brain axis in cirrhosis and resultant impact on patients, caregivers, and the healthcare system.

Figure 2:

Patho-physiological mechanisms by which liver disease and gut alterations impact the brain in cirrhosis

Figure 3:

Gut-brain Axis Changes in Alcohol-related Liver Disease. Red symbols indicate where studies have published a role of gut microbial structure and/or functional change in human disease.