Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases

Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases
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DOI:
10.1073/pnas.0706625104
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发表时间:
2007-08-21
影响因子:
11.1
通讯作者:
Pace, Norman R.
Pace, Norman R.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Frank, Daniel N.;Amand, Allison L. St.;Pace, Norman R.

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克罗恩病(CD)和溃疡性结肠炎(UC)是两种主要的人类炎症性肠病,是以肠道慢性炎症为特征的特发性复发性疾病。虽然有几条推理线索表明胃肠道(GI)微生物影响炎症性肠病(IBD)的发病机制,但涉及的微生物类型尚未得到充分描述。在这里,我们报告了从CD和UC患者以及非IBD对照中获得的GI组织样本的不依赖培养的rRNA序列分析结果。通过手术从各种肠道部位获得标本,包括病理正常和异常状态。我们的研究结果提供了对人类小肠微生物群的全面分子分析。克隆文库的比较揭示了CD和UC患者的微生物群与非lBD对照的微生物群之间的统计学显著差异。值得注意的是,我们的结果表明,CD和UC样本的一个子集含有异常的GI微生物群,其特征在于肠道细菌的消耗,特别是硬革菌门和拟杆菌门的成员。通过GI微生物群对患者进行分层提供了进一步的证据,表明CD代表了一系列疾病状态,并表明通过纠正检测到的微生物失衡可能有助于治疗某些形式的IBD。
The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-lBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmcutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.