Evidence for the butyrate metabolism as key pathway improving ulcerative colitis in both pediatric and adult patients.

Evidence for the butyrate metabolism as key pathway improving ulcerative colitis in both pediatric and adult patients.
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丁酸盐代谢是改善儿童和成人溃疡性结肠炎的关键途径的证据。

DOI:
10.1080/21655979.2021.1985815
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发表时间:
2021-12
期刊:
影响因子:
4.9
通讯作者:
Li M
Li M
中科院分区:
生物学2区
文献类型:
--
作者:
Zhou Z;Cao J;Liu X;Li M

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越来越多的证据表明,儿童和成人溃疡性结肠炎(UC)患者之间的基因谱和途径有许多相似之处和差异。在这项研究中,我们的目的是调查儿童和成人UC肠组织中的共享基因和途径。通过基因表达综合数据集GSE 87473和GSE 126124的生物信息学分析,鉴定了儿童和成人UC之间的差异表达基因(DEG)。使用基因本体和途径富集分析重叠和区分的DEG。基因集变异分析(GSVA)用于对比一致性。采用右旋糖酐硫酸钠(DSS)和啮齿类柠檬酸杆菌诱导小鼠结肠炎模型。从成人UC与成人健康对照组的肠组织中筛选出2616个DEG,从儿科中筛选出1195个DEG。使用重叠DEG富集了儿童和成人UC之间的相同途径,主要与免疫应答和代谢过程相关,包括丁酸盐代谢,这也通过GSVA分析确定。值得注意的是,丁酸盐代谢是这两项分析所富集的唯一下调途径,表明丁酸盐代谢是与儿童和成人UC相关的关键途径之一。此外,丁酸盐抑制DSS诱导的小鼠肠道炎症和柠檬酸杆菌诱导的小鼠肠道炎症。因此,研究表明丁酸盐代谢在儿童和成人UC中均至关重要。丁酸钠对小鼠结肠炎有抑制作用,为丁酸钠治疗UC提供了理论依据。缩略语:UC,溃疡性结肠炎; IBD,炎症性肠病; DEG,差异表达基因; GEO,基因表达综合; SVA,空间变异切趾; LIMMA,微阵列数据的线性模型; FC,倍数变化; GO,基因本体; KEGG,京都基因和基因组百科全书; GSVA,基因集变异分析; MSigDB,分子特征数据库; WT,野生型; DSS,葡聚糖硫酸钠; HC,健康对照; SD,标准差; SNHG 5,小核仁RNA宿主基因5; GLP-2,胰高血糖素样肽2; GSE,基因集富集; ECM,细胞外基质; TCA,三羧酸循环; NA,不可用。
Accumulating evidence has shown many similarities and differences of gene profiles and pathways between pediatric and adult ulcerative colitis (UC) patients. In this study, we aimed to investigate the shared genes and pathways in intestinal tissues of pediatric and adult UC. Differentially expressed genes (DEGs) between pediatric and adult UC were identified via bioinformatic analysis of Gene Expression Omnibus datasets GSE87473 and GSE126124. Gene Ontology and pathway enrichment were used to analyze overlapped and distinguished DEGs. Gene Set Variation Analysis (GSVA) was utilized for contrast consistency. Mice colitis models were induced by dextran sulfate sodium (DSS) and Citrobacter rodentium. 2616 DEGs were screened out in intestinal tissues of adult UC compared with those of adult healthy controls, and 1195 DEGs in pediatrics. Same pathways between pediatric and adult UC were enriched using overlapped DEGs, mainly related to immune responses and metabolic processes, including butyrate metabolism, which was also identified by GSVA analysis. Of note, butyrate metabolism was the exclusive down-regulated pathway enriched by these two analyses, indicating that butyrate metabolism is one of the key pathways associated with both pediatric and adult UC. In addition, butyrate suppressed DSS-induced and Citrobacter rodentium-induced intestinal inflammation in mice. Therefore, the study revealed that butyrate metabolism was critical in both pediatric and adult UC. And butyrate suppressed colitis in mice, which provided a theoretical basis for the potential treatment of butyrate for UC patients. Abbreviations: UC, Ulcerative colitis; IBD, Inflammatory bowel disease; DEGs, Differentially expressed genes; GEO, Gene Expression Omnibus; SVA, Spatial variant apodization; LIMMA, Linear models for the microarray data; FC, Fold change; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; GSVA, Gene Set Variation Analysis; MSigDB, Molecular Signatures Database; WT, Wild-type; DSS, Dextran sulfate sodium; HC, Healthy control; SD, Standard deviation; SNHG5, Small nucleolar RNA host gene 5; GLP-2, Glucagon-like peptide 2; GSE, Gene set enrichment; ECM, Extracellular matrix; TCA, Tricarboxylic acid cycle; NA, Not available.
DOI: 10.1093/ecco-jcc/jjx009
发表时间: 2017-07-01
影响因子: 8
作者:
Harbord, Marcus;Eliakim, Rami;Carbonnel, Franck
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