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

ABSTRACT: 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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9319335 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Cigarette smoking is an important environmental risk factor for cardiovascular events of hypertension (HTN). Existing studies have provided evidence supporting altered gut microbiota by cigarette smoking, especially in hypertensive patients. Metabolic biomarkers play a central role in the functional potentials of the gut microbiome but are poorly characterized in hypertensive smokers. To explore whether serum metabolomics signatures and compositions of HTN patients were varied in smokers, and investigate their connecting relationship to gut microbiota, the serum metabolites were examined in untreated hypertensive patients using untargeted liquid chromatography-mass spectrometry (LC/MS) analysis. Results: A dramatic difference and clear separation in community features of circulating metabolomics members were seen in smoking HTN patients compared with the non-smoking controls, according to partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Serum metabolic profiles and compositions of smoking patients with HTN were significantly distinct from the controls, and were characterized by enrichment of 12-HETE, 7-Ketodeoxycholic acid, Serotonin, N-Stearoyl tyrosine and Deoxycholic acid glycine conjugate, and the depletion of Tetradecanedioic acid, Hippuric acid, Glyceric acid, 20-Hydroxyeicosatetraenoic acid, Phenylpyruvic acid and Capric acid. Additionally, the metabolome displayed prominent functional signatures, with a majority proportion of the metabolites identified to be discriminating between groups distributed in Starch and sucrose metabolism, Caffeine metabolism, Pyruvate metabolism, Glycine, serine and threonine metabolism, and Phenylalanine metabolic pathways. Furthermore, the observation of alterations in metabolites associated with intestinal microbial taxonomy indicated that these metabolic members might mediate the effects of gut microbiome on the smoking host. Indeed, the metabolites specific to smoking HTNs were strongly organized into co-abundance networks, interacting with an array of clinical parameters, including uric acid (UA), low-denstiy lipoprotein cholesterol (LDLC) and smoking index. Conclusions: In conclusion, we demonstrated disparate circulating blood metabolome composition and functional potentials in hypertensive smokers, showing a linkage between specific metabolites in blood and the gut microbiome.

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

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