Mutch David M, Simmering Rainer, Donnicola Dominique, Fotopoulos Grigorios, Holzwarth James A, Williamson Gary, Corthésy-Theulaz Irène
Nestlé Research Center, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland.
Physiol Genomics. 2004 Sep 16;19(1):22-31. doi: 10.1152/physiolgenomics.00105.2004. Epub 2004 Jun 29.
The gastrointestinal tract (GIT) of eukaryotes is colonized by a vast number of bacteria, where the commensal microbiota play an important role in defining the healthy gut. To investigate the influence of commensal bacteria on multiple regions of the host GIT transcriptome, the gene expression profiles of the corpus, jejunum, descending colon, and rectum of conventional (n = 3) and germ-free mice (n = 3) were examined using the Affymetrix Mu74Av2 GeneChip. Differentially regulated genes were identified using the global error assessment model, and a novel method of Gene Ontology (GO) clustering was used to identify significantly modulated biological functions. The microbiota modify the greatest number of genes in the jejunum (267 genes with an alpha < 0.001) and the fewest in the rectum (137 genes with an alpha < 0.001). Clustering genes by GO biological process and molecular function annotations revealed that, despite the large number of differentially regulated genes, the residential microbiota most significantly modified genes involved in such biological processes as immune function and water transport all along the length of the mouse GIT. Additionally, region-specific communication between the host and microbiota were identified in the corpus and jejunum, where tissue kallikrein and apoptosis regulator activities were modulated, respectively. These findings identify important interactions between the microbiota and the mouse gut tissue transcriptome and, furthermore, suggest that interactions between the microbial population and host GIT are implicated in the coordination of region-specific functions.
真核生物的胃肠道(GIT)中定殖着大量细菌,其中共生微生物群在界定健康肠道方面发挥着重要作用。为了研究共生细菌对宿主胃肠道转录组多个区域的影响,使用Affymetrix Mu74Av2基因芯片检测了常规小鼠(n = 3)和无菌小鼠(n = 3)的胃体、空肠、降结肠和直肠的基因表达谱。使用全局误差评估模型鉴定差异调节基因,并采用一种新的基因本体论(GO)聚类方法来鉴定显著调节的生物学功能。微生物群在空肠中调节的基因数量最多(267个基因,α<0.001),在直肠中调节的基因数量最少(137个基因,α<0.001)。通过GO生物学过程和分子功能注释对基因进行聚类分析表明,尽管存在大量差异调节基因,但常驻微生物群对小鼠胃肠道全长中涉及免疫功能和水运输等生物学过程的基因的调节最为显著。此外,在胃体和空肠中发现了宿主与微生物群之间的区域特异性通讯,其中组织激肽释放酶和凋亡调节因子的活性分别受到调节。这些发现确定了微生物群与小鼠肠道组织转录组之间的重要相互作用,并进一步表明微生物群体与宿主胃肠道之间的相互作用与区域特异性功能的协调有关。