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未靶向比较代谢组学分析伴有和不伴有晚发性母乳性黄疸的婴儿。

An untargeted comparative metabolomics analysis of infants with and without late-onset breast milk jaundice.

机构信息

Department of Clinical Nutrition, Peking University People's Hospital, Beijing, China.

Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health, School of Public Health, Peking University, Beijing, China.

出版信息

PLoS One. 2024 Aug 12;19(8):e0308710. doi: 10.1371/journal.pone.0308710. eCollection 2024.

Abstract

BACKGROUND

Late-onset breast milk jaundice (LBMJ) is a common form of hyperbilirubinemia, which can result in serious complications for newborns with persistently high bilirubin levels. The aim of this study was to investigate the differences in fecal metabolites between breastfed infants with and without LBMJ in order to elucidate potential biological mechanisms.

METHODS

Biological samples were collected from 12 infants with LBMJ and 12 healthy individuals. Ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was utilized for non-targeted determination of fecal metabolites. Principal components analysis (PCA), cluster analysis, and differential metabolite analysis were performed in both positive ion mode and negative ion mode for the two groups. Additionally, the KEGG database was employed to comprehensively analyze the pathways of differential metabolites.

RESULTS

There were no significant differences in maternal and neonatal demographic characteristics between the two groups (p > 0.05). The results of PCA and cluster heat map analysis in both modes showed that there were significant differences in metabolites between the two groups. Among 751 differential metabolites (DMs) detected in positive ion mode, 720 were up-regulated in the case group while 31 were down-regulated. In negative ion mode, 1891 DMs were detected, including 817 up-regulated metabolites and 1074 down-regulated metabolites in the case group. Analysis of differential metabolic pathways showed that the DMs of the two groups were mainly annotated and enriched in Biotin metabolism, N-Glycan biosynthesis, Taurine and hypotaurine metabolism, Pyrimidine metabolism, and Pentose and glucuronate interconversions.

CONCLUSION

Significant differences exist in fecal metabolites between LBMJ infants and healthy controls. The study of differential metabolic pathways provides insights into the mechanism of LBMJ.

摘要

背景

晚发型母乳性黄疸(LBMJ)是一种常见的高胆红素血症,对于胆红素持续升高的新生儿,可能会导致严重的并发症。本研究旨在探讨母乳性黄疸患儿与健康对照组粪便代谢物的差异,以阐明潜在的生物学机制。

方法

收集 12 例 LBMJ 患儿和 12 例健康对照者的粪便样本。采用超高效液相色谱-四极杆飞行时间串联质谱(UHPLC-Q-TOF/MS)非靶向法测定粪便代谢物。分别对正、负离子模式下的两组样本进行主成分分析(PCA)、聚类分析和差异代谢物分析。同时,采用 KEGG 数据库对差异代谢物的通路进行全面分析。

结果

两组患儿的母儿一般资料比较差异无统计学意义(P>0.05)。正、负离子模式下 PCA 和聚类热图分析结果均显示两组间代谢物存在明显差异。正离子模式下共检测到 751 个差异代谢物(DMs),其中上调 720 个,下调 31 个;负离子模式下共检测到 1891 个 DMs,其中上调 817 个,下调 1074 个。差异代谢通路分析显示,两组患儿的 DMs 主要注释和富集在生物素代谢、N-聚糖生物合成、牛磺酸和次牛磺酸代谢、嘧啶代谢、戊糖和葡萄糖醛酸相互转化等通路中。

结论

LBMJ 患儿与健康对照组粪便代谢物存在明显差异。差异代谢通路的研究为 LBMJ 的发病机制提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7156/11318923/df3d1376904c/pone.0308710.g001.jpg

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