Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.
Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.
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DOI：
10.1186/s13059-015-0637-x
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发表时间：
2015-04-08
期刊：
影响因子：
12.3
通讯作者：
Huttenhower C
中科院分区：
文献类型：
--
作者：
Morgan XC;Kabakchiev B;Waldron L;Tyler AD;Tickle TL;Milgrom R;Stempak JM;Gevers D;Xavier RJ;Silverberg MS;Huttenhower C
溃疡性结肠炎（UC）回肠贮袋-肛门吻合术（IPAA）后常见贮袋炎。与炎症性肠病（IBD）类似，宿主遗传学和微生物群都参与其发病机制。我们使用IBD的IPAA模型将粘膜宿主基因表达与粘膜微生物组和临床结果相关联。我们分析了来自患有UC和家族性腺瘤性息肉病的IPAA患者的配对活检的宿主转录组数据和16 S rRNA基因测序数据。为了实现全基因组微生物组-转录组关联研究的功效，我们使用主成分分析进行转录本和进化枝减少，并确定进化枝和转录本之间的显著共变。宿主转录物主要与活检位置和炎症共变，而微生物主要与抗生素使用共变。令人惊讶的是，转录物-微生物的关联是适度的，但最强烈的微生物相关的宿主转录物模式富集补体级联基因和白细胞介素-12途径。这些宿主过程的激活与Sutterella，Akkermansia，Biophylla细菌和Roseburia丰度呈负相关，与Escherichia丰度呈正相关。这项研究量化了炎症，抗生素使用和活检位置对结肠袋炎期间微生物组和宿主转录组的影响。了解这些影响对于基本的生物学见解以及设计良好和足够有力的研究至关重要。此外，我们的研究提供了一种使用高通量测序以适当的统计能力分析宿主-微生物相互作用的方法，并表明肠道上皮转录的横截面变化不是结肠袋炎期间宿主-微生物组调控界面的主要组成部分。本文的在线版本（doi：10.1186/s13059-015-0637-x）包含补充材料，可供授权用户使用。
Pouchitis is common after ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC). Similar to inflammatory bowel disease (IBD), both host genetics and the microbiota are implicated in its pathogenesis. We use the IPAA model of IBD to associate mucosal host gene expression with mucosal microbiomes and clinical outcomes. We analyze host transcriptomic data and 16S rRNA gene sequencing data from paired biopsies from IPAA patients with UC and familial adenomatous polyposis. To achieve power for a genome-wide microbiome-transcriptome association study, we use principal component analysis for transcript and clade reduction, and identify significant co-variation between clades and transcripts. Host transcripts co-vary primarily with biopsy location and inflammation, while microbes co-vary primarily with antibiotic use. Transcript-microbe associations are surprisingly modest, but the most strongly microbially-associated host transcript pattern is enriched for complement cascade genes and for the interleukin-12 pathway. Activation of these host processes is inversely correlated with Sutterella, Akkermansia, Bifidobacteria, and Roseburia abundance, and positively correlated with Escherichia abundance. This study quantifies the effects of inflammation, antibiotic use, and biopsy location upon the microbiome and host transcriptome during pouchitis. Understanding these effects is essential for basic biological insights as well as for well-designed and adequately-powered studies. Additionally, our study provides a method for profiling host-microbe interactions with appropriate statistical power using high-throughput sequencing, and suggests that cross-sectional changes in gut epithelial transcription are not a major component of the host-microbiome regulatory interface during pouchitis. The online version of this article (doi:10.1186/s13059-015-0637-x) contains supplementary material, which is available to authorized users.
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影响因子：
3
作者：
Biswas, Shameek;Storey, John D.;Akey, Joshua M.
通讯作者：
Akey, Joshua M.
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影响因子：
3.3
作者：
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DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
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影响因子：
3.7
作者：
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DOI：
10.1073/pnas.97.18.10101
发表时间：
2000-08-29
影响因子：
11.1
作者：
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通讯作者：
Botstein, D