饮食诱导缓解对小儿克罗恩病代谢组学的影响。
Metabolome Changes With Diet-Induced Remission in Pediatric Crohn's Disease.
机构信息
Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Emma Children's Hospital, Amsterdam, the Netherlands.
National Research Council Canada, Human Health Therapeutics, Halifax, Canada.
出版信息
Gastroenterology. 2022 Oct;163(4):922-936.e15. doi: 10.1053/j.gastro.2022.05.050. Epub 2022 Jun 7.
BACKGROUND & AIMS: The Crohn's disease (CD) exclusion diet (CDED) plus partial enteral nutrition (PEN) and exclusive enteral nutrition (EEN) both induce remission in pediatric CD. CDED+PEN is better tolerated and able to sustain remission. We characterized the changes in fecal metabolites induced by CDED+PEN and EEN and their relationship with remission.
METHODS
A total of 216 fecal metabolites were measured in 80 fecal samples at week (W) 0, W6, and W12, of children with mild to moderate CD in a prospective randomized trial comparing CDED+PEN vs EEN. The metabolites were measured using liquid chromatography coupled to mass spectrometry. Metagenome Kyoto Encyclopedia of Genes and Genomes Orthology analysis was performed to investigate the differential functional gene abundance involved in specific metabolic pathways. Data were analyzed according to clinical outcome of remission (W6_rem), no remission (W6_nr), sustained remission (W12_sr), and nonsustained (W12_nsr) remission.
RESULTS
A decrease in kynurenine and succinate synthesis and an increase in N-α-acetyl-arginine characterized CDED+PEN W6_rem, whereas changes in lipid metabolism characterized EEN W6_rem, especially reflected by lower levels in ceramides. In contrast, fecal metabolites in EEN W6_nr were comparable to baseline/W0 samples. CDED+PEN W6_rem children maintained metabolome changes through W12. In contrast, W12_nsr children in the EEN group, who resumed a free diet after week 6, did not. The metabolome of CDED+PEN differed from EEN in the purine, pyrimidine, and sphingolipid pathways. A significant differential abundance in several genes involved in these pathways was detected.
CONCLUSION
CDED+PEN- and EEN-induced remission are associated with significant changes in inflammatory bowel disease-associated metabolites such as kynurenine, ceramides, amino acids, and others. Sustained remission with CDED+PEN, but not EEN, was associated with persistent changes in metabolites.
CLINICALTRIALS
gov, Number NCT01728870.
背景与目的
克罗恩病（CD）排除饮食（CDED）联合部分肠内营养（PEN）和完全肠内营养（EEN）均可诱导儿科 CD 缓解。CDED+PEN 耐受性更好，能维持缓解。我们对 CDED+PEN 和 EEN 诱导的粪便代谢物变化及其与缓解的关系进行了特征描述。
方法
在一项前瞻性随机试验中，比较 CDED+PEN 与 EEN，共纳入 80 例轻至中度 CD 患儿，分别于第 0、6 和 12 周时采集粪便样本，使用液相色谱-质谱联用技术检测 216 种粪便代谢物。采用宏基因组京都基因与基因组百科全书（KEGG）Orthology 分析，对特定代谢途径中涉及的差异功能基因丰度进行研究。根据临床缓解（W6_rem）、未缓解（W6_nr）、持续缓解（W12_sr）和未持续缓解（W12_nsr）的结果对数据进行分析。
结果
CDED+PEN W6_rem 组中犬尿氨酸和琥珀酸合成减少，N-α-乙酰精氨酸增加，而 EEN W6_rem 组中脂质代谢发生变化，主要表现为神经酰胺水平降低。相比之下，EEN W6_nr 组的粪便代谢物与基线/W0 样本相似。CDED+PEN W6_rem 组患儿在 W12 时仍保持代谢组变化。相比之下，EEN 组 W12_nsr 患儿在第 6 周后恢复正常饮食，代谢组未发生变化。CDED+PEN 组和 EEN 组在嘌呤、嘧啶和鞘脂代谢途径上的代谢组存在显著差异。这些途径中多个基因的丰度也存在显著差异。
结论
CDED+PEN 和 EEN 诱导缓解与炎症性肠病相关代谢物（如犬尿氨酸、神经酰胺、氨基酸等）的显著变化相关。CDED+PEN 诱导的缓解持续存在，而 EEN 诱导的缓解则与代谢物的持续变化相关。
临床试验
gov，编号 NCT01728870。
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