A novel stepwise integrative analysis pipeline reveals distinct microbiota-host interactions and link to symptoms in irritable bowel syndrome.
A novel stepwise integrative analysis pipeline reveals distinct microbiota-host interactions and link to symptoms in irritable bowel syndrome.
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DOI：
10.1038/s41598-021-84686-9
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发表时间：
2021-03-09
影响因子：
4.6
通讯作者：
Simrén M
中科院分区：
文献类型：
--
作者：
Polster A;Öhman L;Tap J;Derrien M;Le Nevé B;Sundin J;Törnblom H;Cvijovic M;Simrén M
虽然不完全理解，但假定微生物群-宿主相互作用在肠易激综合征（IBS）中改变。因此，我们的目标是开发一种新的分析管道，专门用于微生物-宿主相互作用和与症状的关联的综合分析，并证明其在试点队列中的实用性。开发了一个多层逐步综合分析管道，以可视化复杂的变量关联。在IBS患者和健康对照（HC）的数据集上展示了管道的应用，使用R软件包分析结肠宿主mRNA和粘膜微生物群（16S rRNA基因测序），以及胃肠道（GI）和心理症状。共纳入42例IBS患者（57%女性，平均年龄33.6岁（范围18 - 58））和20例HC患者（60%女性，平均年龄26.8岁（范围23 - 41））。只有在IBS患者中，Toll样受体4和与屏障功能相关的基因（PAR 2，OCLN，TJP 1）的mRNA表达密切相关，提示潜在的功能关系。这种基于宿主基因的"渗透性簇"与粘膜邻近衣原体和慢球蛋白相关，并且还与饱腹感以及焦虑、抑郁和疲劳相关。在IBS患者和HC中，嗜铬粒蛋白、分泌粒蛋白和TLR聚集在一起。在IBS患者中，这种基于宿主基因的“免疫-肠内分泌簇”与厚壁菌门的特定成员以及抑郁和疲劳相关，而在HC中，未发现与微生物群的显著相关性。我们已经开发了一种逐步综合分析管道，可以识别独特的宿主-微生物群相互关联模式以及与IBS患者症状的关联。这种分析管道可能有助于促进对健康和疾病中复杂变量关联的理解。
Although incompletely understood, microbiota-host interactions are assumed to be altered in irritable bowel syndrome (IBS). We, therefore, aimed to develop a novel analysis pipeline tailored for the integrative analysis of microbiota-host interactions and association to symptoms and prove its utility in a pilot cohort. A multilayer stepwise integrative analysis pipeline was developed to visualize complex variable associations. Application of the pipeline was demonstrated on a dataset of IBS patients and healthy controls (HC), using the R software package to analyze colonic host mRNA and mucosal microbiota (16S rRNA gene sequencing), as well as gastrointestinal (GI) and psychological symptoms. In total, 42 IBS patients (57% female, mean age 33.6 (range 18–58)) and 20 HC (60% female, mean age 26.8 (range 23–41)) were included. Only in IBS patients, mRNA expression of Toll-like receptor 4 and genes associated with barrier function (PAR2, OCLN, TJP1) intercorrelated closely, suggesting potential functional relationships. This host genes-based “permeability cluster” was associated to mucosa-adjacent Chlamydiae and Lentisphaerae, and furthermore associated to satiety as well as to anxiety, depression and fatigue. In both IBS patients and HC, chromogranins, secretogranins and TLRs clustered together. In IBS patients, this host genes-based “immune-enteroendocrine cluster” was associated to specific members of Firmicutes, and to depression and fatigue, whereas in HC no significant association to microbiota was identified. We have developed a stepwise integrative analysis pipeline that allowed identification of unique host-microbiota intercorrelation patterns and association to symptoms in IBS patients. This analysis pipeline may aid in advancing the understanding of complex variable associations in health and disease.
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影响因子：
3.4
作者：
Paveljšek D;Ivičak-Kocjan K;Treven P;Benčina M;Jerala R;Rogelj I
通讯作者：
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作者：
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通讯作者：
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作者：
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