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溃疡性结肠炎和克罗恩病患者肠道菌群失调的标志物。

Markers of dysbiosis in patients with ulcerative colitis and Crohn's disease.

作者信息

Danilova N A, Abdulkhakov S R, Grigoryeva T V, Markelova M I, Vasilyev I Yu, Boulygina E A, Ardatskaya M D, Pavlenko A V, Tyakht A V, Odintsova A Kh, Abdulkhakov R A

机构信息

Kazan Federal University, Kazan, Russia.

Kazan State Medical University of the Ministry of Health of the Russian Federation, Kazan, Russia.

出版信息

Ter Arkh. 2019 May 15;91(4):17-24. doi: 10.26442/00403660.2019.04.000211.

Abstract

AIM

The aim of the study was to study the taxonomic and functional composition of the gut microbiota in ulcerative colitis (UC) and Crohn's disease (CD) patients to identify key markers of dysbiosis in IBD.

MATERIALS AND METHODS

Fecal samples obtained from 95 IBD patients (78 UC and 17 CD) as well as 96 healthy volunteers were used for whole-genome sequencing carried out on the SOLiD 5500 W platform. Taxonomic profiling was performed by aligning the reeds, not maped on hg19, on MetaPhlAn2 reference database. Reeds were mapped using the HUNAnN2 algorithm to the ChocoPhlAn database to assess the representation of microbial metabolic pathways. Short-chain fatty acids (SCFA) level were measured in fecal samples by gas-liquid chromatographic analysis.

RESULTS

Changes in IBD patients gut microbiota were characterized by an increase in the representation of Proteobacteria and Bacteroidetes phyla bacteria and decrease in the number of Firmicutes phylum bacteria and Euryarchaeota phylum archaea; a decrease in the alpha-diversity index, relative representation of butyrate-producing, hydrogen-utilizing bacteria, and Methanobrevibacter smithii; increase in the relative representation of Ruminococcus gnavus in UC and CD patients and Akkermansia muciniphila in CD patients. Reduction of Butyryl-CoA: acetate CoA transferase gene relative representation in CD patients, decrease of absolute content of SCFA total number as well as particular SCFAs and main SCFAs ratio in IBD patients may indicate inhibition of functional activity and number of anaerobic microflora and/or an change in SCFA utilization by colonocytes.

CONCLUSION

the revealed changes can be considered as typical signs of dysbiosis in IBD patients and can be used as potential targets for IBD patients personalized treatment development.

摘要

目的

本研究旨在探究溃疡性结肠炎(UC)和克罗恩病(CD)患者肠道微生物群的分类和功能组成,以确定炎症性肠病(IBD)中生态失调的关键标志物。

材料与方法

从95例IBD患者(78例UC和17例CD)以及96名健康志愿者获取粪便样本,在SOLiD 5500 W平台上进行全基因组测序。通过将未映射到hg19上的reads与MetaPhlAn2参考数据库比对进行分类分析。使用HUNAnN2算法将reads映射到ChocoPhlAn数据库,以评估微生物代谢途径的代表性。通过气液色谱分析测量粪便样本中的短链脂肪酸(SCFA)水平。

结果

IBD患者肠道微生物群的变化特征为变形菌门和拟杆菌门细菌的占比增加,厚壁菌门细菌和广古菌门古菌数量减少;α-多样性指数降低,产丁酸、利用氢气的细菌以及史氏甲烷短杆菌的相对占比降低;UC和CD患者中解木聚糖瘤胃球菌的相对占比增加,CD患者中嗜黏蛋白阿克曼氏菌的相对占比增加。CD患者中丁酰辅酶A:乙酸辅酶A转移酶基因的相对占比降低,IBD患者中SCFA总数的绝对含量以及特定SCFA和主要SCFA比例的降低可能表明厌氧微生物群的功能活性和数量受到抑制,和/或结肠细胞对SCFA的利用发生改变。

结论

所揭示的变化可被视为IBD患者生态失调的典型体征,并可作为开发IBD患者个性化治疗的潜在靶点。

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