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肠道饥饿:肠道衰竭儿童肠道生态系统中丁酸盐的缺乏。

Starving the Gut: A Deficit of Butyrate in the Intestinal Ecosystem of Children With Intestinal Failure.

机构信息

Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.

Department of Medicine and Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.

出版信息

JPEN J Parenter Enteral Nutr. 2020 Aug;44(6):1112-1123. doi: 10.1002/jpen.1715. Epub 2019 Oct 22.

DOI:10.1002/jpen.1715
PMID:31642067
Abstract

BACKGROUND

Intestinal epithelial integrity is influenced by short-chain fatty acids (SCFAs) and is of critical importance for children with intestinal failure (IF) given the known devastating infectious and gastrointestinal complications. The composition of the microbiome in IF represents an important variable in the physiology and prognosis of this disease.

AIM

We sought to compare the intestinal microbiome and SCFA concentration of children who require parenteral nutrition (PN) with that of children with short-bowel syndrome (SBS) who have discontinued PN and with age-matched controls, using high-throughput sequencing to investigate host-microbe interactions.

METHODS

Fifty-three samples were submitted over 6-15 months. Six children with SBS + IF submitted 34 samples, and 6 children with SBS with discontinued PN submitted 15 samples; these were compared with samples from 5 control children. Fecal samples were analyzed by 16S ribosomal RNA partial gene sequencing using the MiSeq Illumina sequencer. SCFAs were measured in stool samples by mass spectrometry.

RESULTS

Butyrate quantity was near absent in children with IF compared with that in controls (median 0.37 nmol/mg vs 10.92 nmol/mg; P < .0001). Similarly, commensal anaerobes known to produce SCFA, including Ruminococcaceae and Lachnospiraceae, were reduced in those with SBS. SBS + IF enteric samples demonstrated a 168-fold increase in the relative abundance of the Escherichia genus seemingly attributable to the species Escherichia coli.

CONCLUSION

The reduced relative abundance of butyrate-producing Clostridia as well as decreased intestinal butyrate concentration in children with IF support further investigation in therapeutic options that target butyrate-producing bacterial communities or butyrate supplementation.

摘要

背景

短链脂肪酸(SCFAs)会影响肠道上皮完整性,对于患有肠衰竭(IF)的儿童尤为重要,因为已知这种疾病会导致严重的感染和胃肠道并发症。IF 患者的微生物组组成是该疾病生理学和预后的一个重要变量。

目的

我们旨在通过高通量测序来研究宿主-微生物相互作用,比较需要接受肠外营养(PN)的儿童与已经停止 PN 的短肠综合征(SBS)儿童以及年龄匹配对照者的肠道微生物组和 SCFA 浓度。

方法

在 6-15 个月的时间内提交了 53 个样本。6 名 SBS+IF 患儿提交了 34 个样本,6 名 SBS 患儿且已停止 PN 提交了 15 个样本;这些样本与 5 名对照患儿的样本进行了比较。使用 MiSeq Illumina 测序仪对粪便样本进行 16S 核糖体 RNA 部分基因测序分析。通过质谱法测量粪便样本中的 SCFA。

结果

与对照组相比,IF 患儿的丁酸量几乎不存在(中位数 0.37 nmol/mg 比 10.92 nmol/mg;P <.0001)。同样,已知产生 SCFA 的共生厌氧菌,包括 Ruminococcaceae 和 Lachnospiraceae,在 SBS 患儿中减少。SBS+IF 肠道样本中,埃希氏菌属的相对丰度增加了 168 倍,似乎归因于物种大肠杆菌。

结论

IF 患儿中丁酸产生菌的相对丰度降低以及肠道丁酸浓度降低支持进一步研究靶向丁酸产生细菌群或丁酸补充的治疗选择。

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