The contributions of bacteria metabolites to the development of hepatic encephalopathy

• Published in: Liver research 2023-12, Vol.7 (4), p.296-303
• Main Authors: Gilbert, Miranda Claire, Setayesh, Tahereh, Wan, Yu-Jui Yvonne
• Format: Article
• Language: English
• Subjects: Bile acid (BA) receptors; Bile acids (BAs); Farnesoid X receptor (FXR); Gut-liver-brain axis; Liver; Takeda G protein-coupled receptor 5 (TGR5)
• ISSN: 2542-5684; 2542-5684
• DOI: 10.1016/j.livres.2022.11.005

Over 20% of mortality during acute liver failure is associated with the development of hepatic encephalopathy (HE). Thus, HE is a complication of acute liver failure with a broad spectrum of neuropsychiatric abnormalities ranging from subclinical alterations to coma. HE is caused by the diversion of portal blood into systemic circulation through portosystemic collateral vessels. Thus, the brain is exposed to intestinal-derived toxic substances. Moreover, the strategies to prevent advancement and improve the prognosis of such a liver-brain disease rely on intestinal microbial modulation. This is supported by the findings that antibiotics such as rifaximin and laxative lactulose can alleviate hepatic cirrhosis and/or prevent HE. Together, the significance of the gut-liver-brain axis in human health warrants attention. This review paper focuses on the roles of bacteria metabolites, mainly ammonia and bile acids (BAs) as well as BA receptors in HE. The literature search conducted for this review included searches for phrases such as BA receptors, BAs, ammonia, farnesoid X receptor (FXR), G protein-coupled bile acid receptor 1 (GPBAR1 or TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), and cirrhosis in conjunction with the phrase hepatic encephalopathy and portosystemic encephalopathy. PubMed, as well as Google Scholar, was the search engines used to find relevant publications.