Abstract
BACKGROUND: Alcohol-Associated Liver Disease (ALD) is a leading cause of liver mortality. Mechanisms responsible for severe ALD and the roles of gut microbiota are not fully understood. Multi-omics tools have enabled a better understanding of metabolic alterations and can aid in identifying metabolites as biomarkers for severe ALD. AIMS: Examine differences between cirrhotic and non-cirrhotic ALD, investigate microbial contributions to such changes, and identify potential diagnostic and prognostic metabolites for severe ALD. METHODS: Untargeted metabolomics were performed on the serum of 11 non-cirrhotic and 11 cirrhotic ALD patients. Data were analyzed using MetOrigin and Metaboanalyst to identify enriched pathways. RESULTS: Increased methylated nucleotides, gamma-glutamyl amino acids, bile acids, and specific metabolites kynurenine and campesterol were increased in ALD cirrhosis, whereas branched-chain amino acids, serotonin, and xanthurenate were decreased. Microbial contributions included increases in the short-chain fatty acid indolebutyrate and methionine sulfoxide in ALD cirrhosis. The analysis also identified the potential for serum levels of 3-ureidopropionate, cis-3,3-methyleneheptanoylglycine, retinol, and valine to be used as biomarkers for clinical assessment of alcohol-associated cirrhosis. CONCLUSION: We have identified a set of metabolites that are differentially altered in cirrhotic compared to non-cirrhotic ALD that can potentially be used as biomarkers for the severity of the disease.