PDF(Pubmed)
Abstract：
Asthma is a multifactorial condition that can be associated with obesity. The phenotypes of asthma in lean and obese patients are different, with proinflammatory signatures being further elevated in the latter. Both obesity and asthma are associated with alterations in intestinal barrier function and immunity, and with the composition of the intestinal microbiota and food consumption. In this study, we aimed to establish an organoid model to test the hypothesis that the intestinal content of lean and obese, allergic, asthmatic children differentially regulates epithelial intestinal gene expression. A model of mouse jejunum intestinal organoids was used. A group of healthy, normal-weight children was used as a control. The intestinal content of asthmatic obese children differentially induced the expression of inflammatory and mitochondrial response genes (Tnf-tumor necrosis factor, Cd14, Muc13-mucin 13, Tff2-Trefoil factor 2 and Tff3, Cldn1-claudin 1 and 5, Reg3g-regenerating family member 3 gamma, mt-Nd1-NADH dehydrogenase 1 and 6, and mt-Cyb-mitochondrial cytochrome b) via the RAGE-advanced glycosylation end product-specific receptor, NF-κB-nuclear factor kappa b and AKT kinase signal transduction pathways. Fecal homogenates from asthmatic normal-weight and obese children induce a differential phenotype in intestinal organoids, in which the presence of obesity plays a major role.
摘要：
哮喘是一种与肥胖相关的多因素疾病。瘦弱和肥胖患者的哮喘表型不同，后者的促炎特征进一步升高。肥胖和哮喘都与肠道屏障功能和免疫力的改变有关。以及肠道微生物群的组成和食物消耗。在这项研究中,我们的目的是建立一个类器官模型来检验瘦和肥胖的肠道含量的假设，过敏,哮喘儿童差异调节上皮肠基因表达。使用小鼠空肠肠类器官的模型。一群健康的人，正常体重儿童用作对照.哮喘肥胖儿童肠道内容物差异诱导炎症和线粒体反应基因表达(Tnf-肿瘤坏死因子,Cd14，Muc13-粘蛋白13，Tff2-三叶因子2和Tff3，Cldn1-claudin1和5，Reg3g-再生家族成员3γ，mt-Nd1-NADH脱氢酶1和6，以及mt-Cyb-线粒体细胞色素b）通过RAGE高级糖基化终产物特异性受体，NF-κB-核因子κB与AKT激酶信号转导通路.哮喘正常体重和肥胖儿童的粪便匀浆在肠道类器官中诱导差异表型，其中肥胖的存在起着重要作用。
