Nod2 is essential for temporal development of intestinal microbial communities
Nod2 is essential for temporal development of intestinal microbial communities
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DOI：
10.1136/gut.2010.216259
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发表时间：
2011-10-01
期刊：
影响因子：
24.5
通讯作者：
Rosenstiel, Philip
中科院分区：
文献类型：
--
作者：
Rehman, Ateequr;Sina, Christian;Rosenstiel, Philip
目的哺乳动物肠道菌群具有高度的多样性，并表现出由宿主基因型和环境因素决定的个体特异性组成。消化道中宿主-微生物稳态的时间发展被认为是免疫系统的主要功能。然而，潜在的细胞和分子机制才刚刚开始显现。核苷酸结合寡聚化结构域2（NOD 2）识别细菌胞壁酰二肽，被认为是肠道屏障的关键传感分子。本研究的目的是探讨其对肠道微生物群的发展和组成的影响，使用Nod 2-缺陷小鼠model.Methods粪便和回肠微生物组成的动力学研究在Nod 2（+/+）和Nod 2（-/-）小鼠在C57 BL/6 J背景。我们使用基于16 S核糖体RNA基因的克隆库测序和高通量焦磷酸测序评估了微生物多样性和组成，并通过实时PCR量化了观察到的变化。在主要细菌门的变化进行了研究，在人类样本中通过定量实时PCR.Results，我们发现，成年Nod 2缺陷小鼠显示出显着改变的微生物群落结构和显着升高的细菌负荷在他们的粪便和回肠末端相比，他们的野生型同行。有趣的是，我们证明这些发现也存在于断奶小鼠中，表明Nod 2对肠道微生物群的早期发育和组成有着深远的影响。我们表明，NOD 2基因型也影响微生物组成在human.Conclusions我们的研究结果点的时间的发展和组成的宿主微生物群，在小鼠和人类，这可能有助于复杂的作用，NOD 2的克罗恩病的病因。
Objective The mammalian commensal gut microbiota is highly diverse and displays an individual-specific composition determined by host genotype and environmental factors. The temporal development of host-microbial homeostasis in the digestive tract is recognised as a major function of the immune system. However, the underlying cellular and molecular mechanisms are just beginning to come to light. Nucleotide-binding, oligomerisation domain 2 (NOD2) recognises bacterial muramyl dipeptide and is regarded as a pivotal sensor molecule of the intestinal barrier. The aim of this study was to investigate its influence on the development and composition of the intestinal microbiota using a Nod2-deficient mouse model.Methods The dynamics of faecal and ileal microbial composition were investigated in Nod2(+/+) and Nod2(-/-) mice on a C57BL/6J background. We assessed microbial diversity and composition using 16S ribosomal RNA gene-based clone library sequencing and high throughput pyrosequencing and quantified the observed changes by real-time PCR. Changes in the major bacterial phyla were investigated in human samples by quantitative real-time PCR.Results We found that adult Nod2-deficient mice display a substantially altered microbial community structure and a significantly elevated bacterial load in their faeces and terminal ileum compared to their wild-type counterparts. Interestingly, we demonstrate that these findings are also present in weaning mice, indicating a profound influence of Nod2 on the early development and composition of the intestinal microbiota. We demonstrate that NOD2 genotypes also influence the microbial composition in humans.Conclusions Our results point to an essential role of Nod2 for the temporal development and composition of the host microbiota, both in mice and in humans, which may contribute to the complex role of NOD2 for the aetiopathogenesis of Crohn's disease.