A critical review of bile acids and their receptors in hepatic encephalopathy

Abstract

Hepatic encephalopathy describes an array of neurological complications that arise due to liver insufficiency. The pathogenesis of hepatic encephalopathy shares a longstanding association with hyperammonemia and inflammation, and recently, aberrant bile acid signaling has been implicated in the development of key features of hepatic encephalopathy. These key features include neuronal dysfunction, neuroinflammation and blood-brain barrier permeability. This review summarizes the findings of recent studies demonstrating a role for bile acids in the pathogenesis of hepatic encephalopathy via one of three main bile acid receptors and speculates on the possible downstream consequences of aberrant bile acid signaling.

Keywords: Cholesterol homeostasis; FXR; Neuroinflammation; Neurosteroids; S1P2R; TGR5.

Figure 1:

Enterohepatic circulation system. Adapted from Bile Acids in Hepatic Encephalopathy. Primary bile acids are synthesized in the liver from hepatocytes and then stored in the gall bladder until needed for digestion. Once bile acids are in the small intestine, they are converted from primary to secondary bile acids by the gut microbiome. Bile acids are then taken into portal circulation and returned to the liver where they can be conjugated with taurine and glycine. Accompanied by a list of bile acids and their classifications.

Figure 2:

FXR signaling response. Modulation of FXR activation can have influences on mood and memory, as well as, playing a role in movement. FXR also plays a large role in cholesterol homeostasis and the production of bile acids. Aberrant bile acid signaling in HE has been observed to impact these pathways.