Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel Syndrome.
Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel Syndrome.
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DOI：
10.3390/metabo12070600
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发表时间：
2022-06-27
期刊：
影响因子：
4.1
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中科院分区：
文献类型：
--
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短肠综合征（SBS）是肠衰竭（IF）的主要原因，可能需要长期肠外营养（PN）支持。然而，长期PN伴随着严重的并发症，如导管相关血流感染（CRBSI）和肠衰竭相关肝病（IFALD），并且与高医疗费用相关。在这项研究中，我们描述了血浆代谢组学特征，并研究了代谢在预测SBS儿科患者长期PN中的作用。在20例接受PN支持的SBS患者的血浆样本中进行了非靶向代谢组学研究：6例患者患有IFALD，14例患者无肝病。作为对照，18例无肝脏或肠道疾病的受试者被纳入分析。与对照组相比，SBS患者具有不同的血浆代谢组学特征，并且与氨基酸代谢和细胞死亡相关的几种途径显著改变。SBS中IFALD的存在与代谢物的改变相关，代谢物主要分类为“氨基酸、肽和类似物”和“苯和衍生物”。血清直接胆红素水平与尿苷、粪臭素和甘草酚水平呈负相关。重要的是，与短期PN组相比，长期PN的SBS患者的谷氨酰胺水平显著升高。最后，使用多变量逻辑回归分析，我们开发了一个预测模型，包括谷氨酰胺和肌酐，以确定需要长期PN支持的儿童SBS患者。这些发现强调了代谢组在SBS伴IF中的潜在关键作用，并表明代谢组学特征可用于长期PN评估。
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.
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