show Abstracthide AbstractThis study explores the link between intestinal microbiome composition, fecal metabolites, and liver disease progression, focusing on butyrate and deoxycholic acid (DCA). The researchers analyzed fecal samples from 308 hospitalized liver disease patients, revealing that advanced liver disease correlates with reduced microbiome diversity and metabolite levels. Patients with higher microbiome diversity and elevated levels of butyrate and DCA were found to have better outcomes, including prolonged transplant-free survival and lower rehospitalization rates. These findings suggest that measuring butyrate and DCA could help identify patients at higher risk for complications, highlighting the metabolites' potential as indicators of liver disease severity.The study emphasizes that butyrate and DCA concentrations decline as liver disease advances, with a corresponding loss of genetic pathways in the microbiome necessary for their production. Unlike traditional microbiome profiling, which can vary across studies, metabolomic profiling of butyrate and DCA provides a more consistent view of microbiome function, potentially enabling rapid identification of at-risk patients. The authors developed a cost-effective, combined assay for butyrate and DCA, which showed strong correlations with liver disease outcomes. This assay allows for faster, more reliable patient assessment, indicating that metabolite levels could serve as a basis for identifying those who might benefit from microbiome-targeted interventions.The study suggests that therapies aiming to reintroduce beneficial metabolites and commensal bacteria, such as fecal microbiota transplants or probiotics, could help restore microbiome functions lost in liver disease. By identifying specific bacteria associated with butyrate and DCA production, the study offers guidance for future therapeutic designs aimed at replenishing these metabolites. However, the authors note that further clinical trials are needed to test these microbiome-targeted therapies' efficacy and safety. Overall, the findings point toward a promising strategy for managing liver disease through microbiome and metabolome restoration, potentially improving patient outcomes by targeting specific deficiencies in microbiome function.