Serum metabolomic analysis in cirrhotic alcohol-associated liver disease patients identified differentially altered microbial metabolites and novel potential biomarkers for disease severity

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 shortchain 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. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.