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小儿肠衰竭患者的多组学分析与肠外营养撤机:一项纵向队列研究。

Multiomics profiling and parenteral nutrition weaning in pediatric patients with intestinal failure: A longitudinal cohort study.

作者信息

Tappauf Niklas, Lamers Yvonne, Sham Ho Pan, Piper Hannah G

机构信息

Food, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, BC, Canada.

British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada.

出版信息

JPEN J Parenter Enteral Nutr. 2025 May;49(4):451-459. doi: 10.1002/jpen.2742. Epub 2025 Mar 4.

DOI:10.1002/jpen.2742
PMID:40035787
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12053138/
Abstract

BACKGROUND

Intestinal failure (IF) is a life-limiting condition that includes a variety of intestinal pathologies. Currently, there are few clinical biomarkers that reflect intestinal function or a patient's potential to wean off parenteral nutrition (PN), making it difficult to predict the clinical trajectory. By associating gut microbiome taxonomic and functional features and blood analytes with the proportion of daily energy delivered via PN-a proxy for intestinal function-our study aimed to discover potential predictors of intestinal function and PN weaning potential.

METHODS

In this longitudinal multiomics cohort study, we followed 18 pediatric patients with IF and PN support for ≤1.5 years. Fecal and stoma samples were analyzed using metagenomic shotgun sequencing to assess bacterial taxonomy and function and internal transcribed spacer 2 ribosomal RNA sequencing to characterize the fungal community. Targeted metabolomics was used to quantify 257 blood analytes. Linear mixed models were used to analyze the associations of PN dependence with microbiome features and blood analytes.

RESULTS

The bacterial and fungal taxonomic composition exhibited substantial interpatient and intrapatient variability, with no link to PN dependence. In contrast, bacterial functional analysis revealed 63 MetaCyc pathways significantly associated with PN dependence. Additionally, 32 blood analytes were associated with PN dependence.

CONCLUSION

In this exploratory study, we found that functional microbiome features and blood metabolomic profiles-particularly urea cycle metabolites, creatinine, asparagine, and tryptophan-derived metabolites-show promise for predicting intestinal function. Furthermore, they may have therapeutic implications for promoting intestinal adaptation. Confirmatory trials with larger sample sizes are needed to validate these findings.

摘要

背景

肠衰竭(IF)是一种危及生命的疾病,包括多种肠道病变。目前,反映肠道功能或患者停用肠外营养(PN)潜力的临床生物标志物很少,这使得预测临床病程变得困难。通过将肠道微生物群分类和功能特征以及血液分析物与通过PN提供的每日能量比例(肠道功能的一个指标)相关联,我们的研究旨在发现肠道功能和PN断奶潜力的潜在预测指标。

方法

在这项纵向多组学队列研究中,我们对18名接受IF和PN支持≤1.5年的儿科患者进行了随访。使用宏基因组鸟枪法测序分析粪便和造口样本,以评估细菌分类和功能,并使用内转录间隔区2核糖体RNA测序来表征真菌群落。靶向代谢组学用于量化257种血液分析物。线性混合模型用于分析PN依赖性与微生物群特征和血液分析物之间的关联。

结果

细菌和真菌的分类组成在患者之间和患者体内表现出很大的变异性,与PN依赖性无关。相比之下,细菌功能分析揭示了63条MetaCyc途径与PN依赖性显著相关。此外,32种血液分析物与PN依赖性相关。

结论

在这项探索性研究中,我们发现功能性微生物群特征和血液代谢组学特征——特别是尿素循环代谢物、肌酐、天冬酰胺和色氨酸衍生代谢物——在预测肠道功能方面显示出前景。此外,它们可能对促进肠道适应具有治疗意义。需要更大样本量的验证试验来证实这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7f/12053138/b2f6ac236c3b/JPEN-49-451-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7f/12053138/b2f6ac236c3b/JPEN-49-451-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7f/12053138/b2f6ac236c3b/JPEN-49-451-g001.jpg

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本文引用的文献

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Microbiome changes under enteral deprivation are dynamic and dependent on intestinal location.肠内营养剥夺下微生物组的变化是动态的,并取决于肠道位置。
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