Metaproteomics of fecal samples of Crohn's disease and Ulcerative Colitis

Metaproteomics of fecal samples of Crohn's disease and Ulcerative Colitis
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DOI:
10.1016/j.jprot.2019.04.009
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发表时间:
2019-06-15
影响因子:
3.3
通讯作者:
Heyer, R.
Heyer, R.
中科院分区:
生物学2区
文献类型:
--
作者:
Lehmann, T.;Schallert, K.;Heyer, R.

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克罗恩病(CD)和溃疡性结肠炎(UC)是胃肠道的慢性炎症性肠病(IBD)。本研究采用非侵入性LC-MS/MS寻找疾病特异性微生物和人类蛋白,这些蛋白可能在以后用于更容易的诊断。因此,我们对17名健康对照组、11名乳糜泻患者和14名UC患者以及13名肠易激病(IBS)患者、8名结肠腺瘤(CA)患者和8名胃癌(GCA)患者进行了调查。用液体苯酚在球磨机中从粪便样品中提取蛋白质。随后,蛋白质被消化成多肽,并通过Orbitrap LC-MS/MS进行分析。使用MetaProteomeAnalyzer软件进行蛋白质鉴定和分类和功能结果的解释。聚类分析和非参数检验(相似性分析)将健康对照者与CD和UC患者以及GCA患者分开。其中,CD和UC与中性粒细胞胞外陷阱和免疫球蛋白G (IgG)的增加有关。此外,在CD和UC中发现人IgA和来自脆弱芽孢杆菌的转录调节蛋白RprY的减少。粪便中乳糜泻的一个特异性标记物是人酶蔗糖-异麦芽糖酶的增加。意义:克罗恩病和溃疡性结肠炎是胃肠道慢性炎症性疾病,诊断需要结肠镜检查等综合医学检查。肠道微生物群落对这些疾病发病机制的影响尚不清楚。因此,本研究通过元蛋白质组方法研究了肠道微生物组对这些疾病的影响,揭示了几种疾病特异性标记蛋白。总的来说,这表明粪便宏蛋白质组学有可能成为一种更好、更容易诊断这两种疾病的非侵入性工具。
Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel diseases (IBD) of the gastrointestinal tract. This study used non-invasive LC-MS/MS to find disease specific microbial and human proteins which might be used later for an easier diagnosis.Therefore, 17 healthy controls, 11 CD patients and 14 UC patients but also 13 Irritable Bowel Disease (IBS) patients, 8 Colon Adenoma (CA) patients, and 8 Gastric Carcinoma (GCA) patients were investigated. The proteins were extracted from the fecal samples with liquid phenol in a ball mill. Subsequently, the proteins were digested tryptically to peptides and analyzed by an Orbitrap LC-MS/MS. For protein identification and interpretation of taxonomic and functional results, the MetaProteomeAnalyzer software was used.Cluster analysis and non-parametric test (analysis of similarities) separated healthy controls from patients with CD and UC as well as from patients with GCA. Among others, CD and UC correlated with an increase of neutrophil extracellular traps and immune globulins G (IgG). In addition, a decrease of human IgA and the transcriptional regulatory protein RprY from Bacillus fragilis was found for CD and UC. A specific marker in feces for CD was an increased amount of the human enzyme sucrose-isomaltase.Significance: Crohn's Disease and Ulcerative Colitis are chronic inflammatory diseases of the gastrointestinal tract, whose diagnosis required comprehensive medical examinations including colonoscopy. The impact of the microbial communities in the gut on the pathogenesis of these diseases is poorly understood. Therefore, this study investigated the impact of gut microbiome on these diseases by a metaproteome approach, revealing several disease specific marker proteins. Overall, this indicated that fecal metaproteomics has the potential to be useful as non-invasive tool for a better and easier diagnosis of both diseases.