Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model.
Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model.
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DOI：
10.1038/ncomms8806
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发表时间：
2015-08-04
影响因子：
16.6
通讯作者：
Finlay BB
中科院分区：
文献类型：
--
作者：
Brown EM;Wlodarska M;Willing BP;Vonaesch P;Han J;Reynolds LA;Arrieta MC;Uhrig M;Scholz R;Partida O;Borchers CH;Sansonetti PJ;Finlay BB
环境性肠病（EE）是一种亚临床慢性小肠炎性疾病，对全球儿童营养不良的持续存在有深远的影响。然而，该疾病的病因仍然未知，迄今为止还没有动物模型，其创建将有助于理解这种复杂的疾病。在这里，我们证明，早期生活消费的中度营养不良的饮食，结合反复口服暴露于大肠杆菌类杆菌和大肠杆菌，重塑小鼠小肠类似于在人类中观察到的EE的功能。我们进一步报告了营养不良对小肠微生物群、代谢物和上皮内淋巴细胞组成的深刻变化，沿着对肠道感染的易感性。我们的研究结果提供的证据表明，饮食和微生物联合收割机有助于EE的病因，并描述了一种新的小鼠模型，可用于阐明这种未充分研究的疾病背后的机制。环境性肠病是一种导致全球儿童营养不良持续存在的小肠疾病。在这里，布朗等人在小鼠中表明，早期生活营养不良，加上暴露于肠道细菌，重塑小肠，以类似于疾病的特征。
Environmental enteropathy (EE) is a subclinical chronic inflammatory disease of the small intestine and has a profound impact on the persistence of childhood malnutrition worldwide. However, the aetiology of the disease remains unknown and no animal model exists to date, the creation of which would aid in understanding this complex disease. Here we demonstrate that early-life consumption of a moderately malnourished diet, in combination with iterative oral exposure to commensal Bacteroidales species and Escherichia coli, remodels the murine small intestine to resemble features of EE observed in humans. We further report the profound changes that malnutrition imparts on the small intestinal microbiota, metabolite and intraepithelial lymphocyte composition, along with the susceptibility to enteric infection. Our findings provide evidence indicating that both diet and microbes combine to contribute to the aetiology of EE, and describe a novel murine model that can be used to elucidate the mechanisms behind this understudied disease. Environmental enteropathy is a disorder of the small intestine that contributes to the persistence of childhood malnutrition worldwide. Here, Brown et al. show in mice that early-life malnourishment, in combination with exposure to commensal bacteria, remodels the small intestine to resemble features of the disease.