Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease.
Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease.
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DOI：
10.1186/1471-230x-13-113
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发表时间：
2013-07-11
影响因子：
2.4
通讯作者：
Satokari R
中科院分区：
文献类型：
--
作者：
Cheng J;Kalliomäki M;Heilig HG;Palva A;Lähteenoja H;de Vos WM;Salojärvi J;Satokari R
乳糜泻（CD）是一种小肠自身免疫性疾病，在遗传易感性（HLA-DQ2/DQ8阳性）个体中由饮食麸质引发。只有一小部分HLA-DQ2/DQ8阳性个体发展为乳糜泻，这表明其他因素在该疾病中起作用。一些研究已经解决了儿童乳糜泻的肠道微生物群异常，但结果不一致。先前，我们证实，与健康对照（HC）相比，儿科CD患者的十二指肠TLR2表达较低，而TLR9表达较高，这表明微生物群可能在CD中发挥作用。我们使用细菌系统发育芯片全面分析了CD （n = 10）和HC （n = 9）儿童十二指肠活检中的微生物群。采用qRT-PCR技术，对无麸质饮食的CD和HC儿童以及治疗过的CD成人（T-CD, n = 6）中选定的粘膜相关基因的表达进行了评估。在CD和HC之间，微生物群的总体组成、多样性和估计的微生物相关分子模式（MAMP）含量是相当的，但在HC和CD之间，由8个属样细菌群组成的亚种群谱存在显著差异。在HC中，TLR2表达的增加与紧密连接蛋白ZO-1的表达呈正相关。在CD和T-CD中，IL-10、IFN-g和CXCR6的表达均高于HC。结果表明，微生物群和粘膜受体表达的改变在CD中起作用。在CD受试者中，IL-10和IFN-g表达的增加可能部分是由于TLR9表达和信号传导的增加。
Celiac disease (CD) is an autoimmune disorder of the small intestine which is triggered by dietary gluten in genetically predisposed (HLA-DQ2/DQ8 positive) individuals. Only a fraction of HLA-DQ2/DQ8 positive individuals develop CD indicating that other factors have a role in the disorder. Several studies have addressed intestinal microbiota aberrancies in pediatric CD, but the results are inconsistent. Previously, we demonstrated that pediatric CD patients have lower duodenal expression of TLR2 and higher expression of TLR9 as compared to healthy controls (HC) indicating that microbiota may have a role in CD. We used bacterial phylogenetic microarray to comprehensively profile the microbiota in duodenal biopsies of CD (n = 10) and HC (n = 9) children. The expression of selected mucosa-associated genes was assessed by qRT-PCR in CD and HC children and in treated CD adults (T-CD, n = 6) on gluten free diet. The overall composition, diversity and the estimated microbe associated molecular pattern (MAMP) content of microbiota were comparable between CD and HC, but a sub-population profile comprising eight genus-like bacterial groups was found to differ significantly between HC and CD. In HC, increased TLR2 expression was positively correlated with the expression of tight junction protein ZO-1. In CD and T-CD, the expression of IL-10, IFN-g and CXCR6 were higher as co5mpared to HC. The results suggest that microbiota and altered expression of mucosal receptors have a role in CD. In CD subjects, the increased expression of IL-10 and IFN-g may have partly resulted from the increased TLR9 expression and signaling.