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一种用于预测克罗恩病患者上消化道受累情况的新型宏基因组生物标志物的开发

Development of a Novel Metagenomic Biomarker for Prediction of Upper Gastrointestinal Tract Involvement in Patients With Crohn's Disease.

作者信息

Kwak Min Seob, Cha Jae Myung, Shin Hyun Phil, Jeon Jung Won, Yoon Jin Young

机构信息

Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, South Korea.

出版信息

Front Microbiol. 2020 Jun 3;11:1162. doi: 10.3389/fmicb.2020.01162. eCollection 2020.

Abstract

The human gut microbiota is an important component in the pathogenesis of Crohn's disease (CD), promoting host-microbe imbalances and disturbing intestinal and immune homeostasis. We aimed to assess the potential clinical usefulness of the colonic tissue microbiome for obtaining biomarkers for upper gastrointestinal (UGI) tract involvement in CD. We analyzed colonic tissue samples from 26 CD patients (13 with and 13 without UGI involvement at diagnosis) from the Inflammatory Bowel Disease Multi-Omics Database. QIIME1, DiTaxa, linear discriminant analysis effect size (LEfSe), and PICRUSt2 methods were used to examine microbial dysbiosis. Linear support vector machine (SVM) and random forest classifier (RF) algorithms were used to identify the UGI tract involvement-associated biomarkers. There were no statistically significant differences in community richness, phylogenetic diversity, and phylogenetic distance between the two groups of CD patients. DiTaxa analysis predicted significant association of the species with UGI involvement, which was confirmed by the LEfSe analysis ( = 0.025). For the feature ranking method in both linear SVM and RF models, the species and age at diagnosis contributed to the combined models. The L-methionine biosynthesis III ( = 0.038) and palmitate biosynthesis II ( = 0.050) were under-represented in CD with UGI involvement. These findings suggest that might serve as a novel potential biomarker for UGI involvement in CD and its correlations, in addition to a range of bacterial species. The mechanisms of interaction between hosts and should be further investigated.

摘要

人类肠道微生物群是克罗恩病(CD)发病机制中的一个重要组成部分,它会促进宿主与微生物之间的失衡,并扰乱肠道和免疫稳态。我们旨在评估结肠组织微生物群在获取CD患者上消化道(UGI)受累生物标志物方面的潜在临床实用性。我们分析了来自炎症性肠病多组学数据库的26例CD患者的结肠组织样本(13例在诊断时有UGI受累,13例无UGI受累)。使用QIIME1、DiTaxa、线性判别分析效应大小(LEfSe)和PICRUSt2方法来检查微生物失调情况。使用线性支持向量机(SVM)和随机森林分类器(RF)算法来识别与UGI受累相关的生物标志物。两组CD患者在群落丰富度、系统发育多样性和系统发育距离方面没有统计学上的显著差异。DiTaxa分析预测该物种与UGI受累存在显著关联,这一结果得到了LEfSe分析的证实(P = 0.025)。对于线性SVM和RF模型中的特征排名方法,该物种和诊断时的年龄对组合模型有贡献。L-蛋氨酸生物合成III(P = 0.038)和棕榈酸生物合成II(P = 0.050)在有UGI受累的CD患者中表达不足。这些发现表明,除了一系列细菌物种外,该物种可能是UGI受累于CD及其相关性的一种新的潜在生物标志物。宿主与该物种之间的相互作用机制应进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1306/7283919/e8620461c826/fmicb-11-01162-g001.jpg

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