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早产儿生长不良与肠道微生物和循环细胞因子。

Gut Microbes and Circulating Cytokines in Preterm Infants with Growth Failure.

机构信息

Department of Pediatrics, Division of Neonatology and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA; The University of California Los Angeles Children's Discovery and Innovation Institute, University of California Los Angeles, Los Angeles, CA, USA.

Department of Pediatrics, Division of Neonatology and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA; The University of California Los Angeles Children's Discovery and Innovation Institute, University of California Los Angeles, Los Angeles, CA, USA.

出版信息

J Nutr. 2023 Jan;153(1):120-130. doi: 10.1016/j.tjnut.2022.10.005. Epub 2022 Dec 20.

Abstract

BACKGROUND

Growth failure (GF) is a multifactorial problem in preterm infants. The intestinal microbiome and inflammation may contribute to GF.

OBJECTIVES

This study's objective was to compare the gut microbiome and plasma cytokines in preterm infants with and without GF.

METHODS

This was a prospective cohort study of infants with birth weights of <1750 g. Infants with a weight or length z-score change from birth to discharge or death that was less than or equal to -0.8 (GF group) were compared with infants without GF [control (CON) group]. The primary outcome was the gut microbiome (at weeks 1-4 of age), assessed by 16S rRNA gene sequencing using Deseq2. Secondary outcomes included inferred metagenomic function and plasma cytokines. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States determined metagenomic function, which was compared using ANOVA. Cytokines were measured by 2-multiplexed immunometric assays and compared using Wilcoxon tests and linear mixed models.

RESULTS

GF (n = 14) and CON group (n = 13) had similar median (IQR) birth weight (1380 [780-1578] g vs. 1275 [1013-1580] g) and gestational age (29 [25-31] weeks vs. 30 [29-32] weeks). Compared with the CON group, the GF group had a greater abundance of Escherichia/Shigella in weeks 2 and 3, Staphylococcus in week 4, and Veillonella in weeks 3 and 4 (P-adjusted < 0.001 for all). Plasma cytokine concentrations did not differ significantly between the cohorts. When all time points are combined, fewer microbes were involved in TCA cycle activity in the GF group compared with the CON group (P = 0.023).

CONCLUSIONS

In this study, when compared with CON infants, GF infants had a distinct microbial signature with increased Escherichia/Shigella and Firmicutes and fewer microbes associated with energy production at later weeks of hospitalization. These findings may suggest a mechanism for aberrant growth.

摘要

背景

生长迟缓(GF)是早产儿的一个多因素问题。肠道微生物组和炎症可能导致 GF。

目的

本研究旨在比较有和无 GF 的早产儿的肠道微生物组和血浆细胞因子。

方法

这是一项对出生体重<1750g 的婴儿进行的前瞻性队列研究。体重或长度 z 评分从出生到出院或死亡的变化小于或等于-0.8(GF 组)的婴儿与无 GF 的婴儿(对照组[CON])进行比较。主要结局是肠道微生物组(在 1-4 周龄时),通过使用 Deseq2 的 16S rRNA 基因测序进行评估。次要结局包括推断的宏基因组功能和血浆细胞因子。通过重建未观察到的状态的群落系统发育分析确定宏基因组功能,使用 ANOVA 进行比较。通过 2 多重免疫计量测定法测量细胞因子,并使用 Wilcoxon 检验和线性混合模型进行比较。

结果

GF(n=14)和 CON 组(n=13)的中位(IQR)出生体重(1380[780-1578]g 与 1275[1013-1580]g)和胎龄(29[25-31]周与 30[29-32]周)相似。与 CON 组相比,GF 组在第 2 和第 3 周时埃希氏菌/志贺氏菌的丰度更高,第 4 周时葡萄球菌丰度更高,第 3 和第 4 周时韦荣球菌丰度更高(所有 P 调整值均<0.001)。两组间血浆细胞因子浓度无显著差异。当所有时间点合并时,与 CON 组相比,GF 组中与三羧酸循环活性相关的微生物数量较少(P=0.023)。

结论

在这项研究中,与 CON 婴儿相比,GF 婴儿的肠道微生物特征明显不同,在住院后期埃希氏菌/志贺氏菌和厚壁菌增多,与能量产生相关的微生物减少。这些发现可能提示了生长不良的机制。

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