Gut Microbiota at the Intersection of Alcohol, Brain, and the Liver

Abstract

Over the last decade, increased research into the cognizance of the gut-liver-brain axis in medicine has yielded powerful evidence suggesting a strong association between alcoholic liver diseases (ALD) and the brain, including hepatic encephalopathy or other similar brain disorders. In the gut-brain axis, chronic, alcohol-drinking-induced, low-grade systemic inflammation is suggested to be the main pathophysiology of cognitive dysfunctions in patients with ALD. However, the role of gut microbiota and its metabolites have remained unclear. Eubiosis of the gut microbiome is crucial as dysbiosis between autochthonous bacteria and pathobionts leads to intestinal insult, liver injury, and neuroinflammation. Restoring dysbiosis using modulating factors such as alcohol abstinence, promoting commensal bacterial abundance, maintaining short-chain fatty acids in the gut, or vagus nerve stimulation could be beneficial in alleviating disease progression. In this review, we summarize the pathogenic mechanisms linked with the gut-liver-brain axis in the development and progression of brain disorders associated with ALD in both experimental models and humans. Further, we discuss the therapeutic potential and future research directions as they relate to the gut-liver-brain axis.

Keywords: alcohol; alcoholic liver disease; bacterial metabolites; gut–liver–brain axis.

Figure 1

Gut–liver–brain axis in alcohol use disorder. Abbreviations: ↑ indicates an increase in the condition or level; MAMPS, microbe-associated molecular patterns; BBB, blood–brain barrier.