Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel...

Short bowel syndrome (SBS) is a major cause of intestinal failure (IF) that may require long-term parenteral nutrition (PN) support. However, long-term PN is accompanied by severe complications such as catheter-related blood stream infection (CRBSI) and intestinal failure-associated liver disease (IFALD), and it is associated with high healthcare costs. In this study, we characterized the plasma metabolomic profile and investigated the role of metabolism in predicting long-term PN in pediatric patients with SBS. Untargeted metabolomics was performed in plasma samples from 20 SBS patients with PN support: 6 patients had IFALD and 14 patients had no liver disease. As controls, 18 subjects without liver or intestinal diseases were included for the analysis. SBS patients had distinct plasma metabolomic signatures compared to controls, and several pathways associated with amino acid metabolism and cell death were significantly changed. The presence of IFALD in SBS was associated with alterations of metabolites mainly classified as "amino acids, peptides, and analogues" and "benzene and derivatives". Serum direct bilirubin levels were negatively correlated with levels of uridine, skatole, and glabrol. Importantly, SBS patients with long-term PN showed significantly increased levels of glutamine compared to those in the short-term PN group. Finally, using multivariate logistic regression analysis, we developed a prediction model including glutamine and creatinine to identify pediatric SBS patients who need long-term PN support. These findings underscore the potential key role of the metabolome in SBS with IF and suggest that metabolomic profiles could be used in long-term PN assessment.