Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis 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, although 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 microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.

中文翻译：

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炎症性肠病肠道微生物组中转录的动力学。

炎症性肠病（IBD）是一组消化道慢性疾病，影响着全球数百万人。遗传，环境和微生物因素与IBD的发作和恶化有关。但是，与肠道微生物失活和异常免疫反应相关的机制仍是未知之数。整合人类微生物组计划试图通过分析疾病中微生物组功能的动态，通过分析在1年内采样的100多个个体的肠道微生物组，来缩小这些差距。在这里，我们基于78个配对的粪便元基因组和元转录组，以及来自59例克罗恩病，34例溃疡性结肠炎和24例非IBD对照患者的222个其他基因组，给出了第一个结果。我们证明了在几种情况下，相对于功能潜力的宏基因组学资料，发炎的肠道中微生物基因表达的测量值可以提供信息。首先，尽管许多微生物表现出一致的DNA和RNA丰度，但我们还检测到了转录活性中物种特异性的偏差，揭示了每个宿主的单个微生物（例如Faecalibacterium prausnitzii）的主要途径转录。因此，这些生物的丧失可能比其基因组丰度所暗示的后果更为深远。此外，我们鉴定了在基因组上丰富但在肠道中无活性或处于休眠状态而几乎没有表达或没有表达的生物（例如Dialister invisus）。最后的，某些特定疾病的微生物特征在转录本水平上更为明显或仅可检测到，例如在IBD患者中主要由不同生物体表达的途径（例如，拟杆菌（Bacteroides vulgatus）和腐臭菌（Alistipes putredinis）。这提供了对肠道微生物途径转录的潜在见解，该途径可能随时间变化，从而诱导表型变化，这些变化与宏基因组学丰度相关。这项研究的结果突出了分析肠道微生物的活性和存在的力量，以深入了解微生物组在IBD中的作用。这提供了对肠道微生物途径转录的潜在见解，该途径可能随时间变化，从而诱导表型变化，这些变化与宏基因组学丰度相关。这项研究的结果突出了分析肠道微生物的活性和存在的力量，以深入了解微生物组在IBD中的作用。这提供了对肠道微生物途径转录的潜在见解，该途径可能随时间变化，从而诱导表型变化，这些变化与宏基因组学丰度相关。这项研究的结果突出了分析肠道微生物的活性和存在的力量，以深入了解微生物组在IBD中的作用。