Laboratoire d'excellence Inflamex, Université Paris-Diderot Sorbonne Paris-Cité, France.
INSERM, UMR 1149, F-75018 Paris, France.
J Crohns Colitis. 2016 Dec;10(12):1428-1436. doi: 10.1093/ecco-jcc/jjw095. Epub 2016 May 4.
Crohn's disease [CD] is a complex disorder characterised by an inappropriate immune response, impaired barrier function and microbial dysbiosis. Mutations in nucleotide oligomeriation domain 2 [NOD2] are CD risk factors. Increase of intestinal permeability, CD4 T cell infiltration, and bacterial dysbiosis are also seen in Nod2-knockout [Nod2 ] mice. However, the specificity and relationship between these Nod2-associated abnormalities remain largely unexplored.
Wild-type [WT], Nod1-knockout [Nod1 ] and Nod2 mice were analysed in parallel. Microbial composition was defined by 454-pyrosequencing of bacterial 16S rRNA genes. Mucin and antimicrobial peptide expression was assessed by RT-PCR. Cell populations from Peyer's patches were determined by flow cytometry. Ussing chambers were used to measure intestinal permeability and bacterial translocation. Finally, to explore the impact of colonisation with mother's microbiota at birth, analyses were also performed in Nod2 and WT mice born from WT surrogate mothers after embryo transfer.
Nod2 mice exhibited colonic bacterial dysbiosis different from WT and Nod1 mice. Altered expression of antimicrobial peptides and mucins in ileum and colon was associated with the microbial composition. Bacterial composition of Nod2 and WT mice obtained by embryo transfer was similar to that observed in Nod2 mice, arguing for a dominant effect of Nod2 -associated dysbiosis. In contrast, increased levels of CD4 T cells and gut barrier defects across Peyer's patches were specific to Nod2 deficiency and independent of Microbial dysbiosis.
Nod2 deficiency is associated with a specific dominant dysbiosis which does not drive mucosal tissue and immune alterations.
克罗恩病（CD）是一种复杂的疾病，其特征为免疫反应异常、屏障功能受损和微生物失调。核苷酸寡聚化结构域 2（NOD2）的突变是 CD 的危险因素。Nod2 敲除（Nod2）小鼠也可见肠道通透性增加、CD4 T 细胞浸润和细菌失调。然而，这些与 Nod2 相关的异常的特异性和关系在很大程度上仍未得到探索。
同时分析野生型（WT）、Nod1 敲除（Nod1）和 Nod2 小鼠。通过 454 焦磷酸测序分析细菌 16S rRNA 基因来定义微生物组成。通过 RT-PCR 评估粘蛋白和抗菌肽的表达。通过流式细胞术测定派尔集合淋巴结中的细胞群。使用 Ussing 室测量肠道通透性和细菌易位。最后，为了探索出生时定植母体微生物群的影响，还在通过胚胎移植从 WT 代孕母亲获得的 Nod2 和 WT 小鼠中进行了分析。
Nod2 小鼠表现出与 WT 和 Nod1 小鼠不同的结肠细菌失调。回肠和结肠中抗菌肽和粘蛋白表达的改变与微生物组成有关。通过胚胎移植获得的 Nod2 和 WT 小鼠的细菌组成与 Nod2 小鼠观察到的相似，这表明 Nod2 相关失调具有主导作用。相比之下，Peyer 集合淋巴结中 CD4 T 细胞水平升高和肠道屏障缺陷是 Nod2 缺乏所特有的，且独立于微生物失调。
Nod2 缺乏与特定的主导失调相关，而不会引起黏膜组织和免疫改变。
