Dynamics of metatranscription in the inflammatory bowel disease gut microbiome.
Dynamics of metatranscription in the inflammatory bowel disease gut microbiome.
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DOI：
10.1038/s41564-017-0089-z
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发表时间：
2018-03
影响因子：
28.3
通讯作者：
Huttenhower C
中科院分区：
文献类型：
--
作者：
Schirmer M;Franzosa EA;Lloyd-Price J;McIver LJ;Schwager R;Poon TW;Ananthakrishnan AN;Andrews E;Barron G;Lake K;Prasad M;Sauk J;Stevens B;Wilson RG;Braun J;Denson LA;Kugathasan S;McGovern DPB;Vlamakis H;Xavier RJ;Huttenhower C
炎症性肠病（IBD）是一组影响全球数百万人的消化道慢性疾病。遗传、环境和微生物因素与IBD的发病和加重有关。然而，与肠道微生物生态失调和异常免疫反应相关的机制在很大程度上仍然未知。综合性人类微生物组项目（iHMP）旨在通过分析一年内采样的100多个人的肠道微生物组来检查疾病中微生物组功能的动态来缩小这些差距。在这里，我们基于来自59例克罗恩病（CD）、34例溃疡性结肠炎（UC）和24例非IBD对照患者的78对粪便宏基因组/元转录组和222个额外的宏基因组呈现了第一个结果。我们展示了几种情况下，在发炎的肠道微生物基因表达的措施可以提供信息相对于宏基因组功能潜力的配置文件。首先，虽然许多微生物生物表现出一致的DNA和RNA丰度，但我们还检测到转录活性的物种特异性偏差，揭示了每个宿主的单个微生物（例如普氏粪杆菌）的主要转录途径。因此，这些生物体在疾病中的损失可能会产生比其基因组丰度所暗示的更深远的后果。此外，我们鉴定了宏基因组丰富但在肠道中无活性或休眠的生物体，其表达很少或没有表达（例如，Dialister invisus）。最后，某些疾病特异性微生物特征更明显或仅在转录水平上可检测到，例如IBD患者中主要由不同生物体表达的途径（例如普通拟杆菌和腐败Alistipes putredinis）。这为肠道微生物途径转录提供了潜在的见解，该转录可以随时间变化，诱导与宏基因组丰度相关的表型变化互补的表型变化。该研究的结果强调了分析肠道微生物的活性和存在的优势，以深入了解微生物组在IBD中的作用。
Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract affecting millions of people worldwide. Genetic, environmental and microbial factors have been implicated in onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project (iHMP) seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of more than 100 individuals sampled over a one year period. Here, we present the first results based on 78 paired fecal metagenomes/metatranscriptomes and 222 additional metagenomes from 59 Crohn’s disease (CD), 34 ulcerative colitis (UC), and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, while many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microbes per host (e.g. by Faecalibacterium prausnitzii). Therefore, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Further, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (e.g. Dialister invisus). Lastly, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways predominantly expressed by different organisms in IBD patients (e.g. Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypic changes complementary to those linked to metagenomic abundances. The study’s results highlight the strength of analyzing both the activity and presence of gut microbes to provide insight into the role of the microbiome in IBD.
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