ZIEL Research Center for Nutrition and Food Science, CDD Center for Diet and Disease, Technische Universität München, Freising-Weihenstephan, Germany.
Inflamm Bowel Dis. 2013 May;19(6):1285-94. doi: 10.1097/MIB.0b013e318281f573.
Enteral nutrition is used to treat a subset of patients with inflammatory bowel diseases. Because dietary factors may contribute to an aggressive immune response toward the intestinal microbiota in the disease susceptible host, we used TNFΔARE/WT mice to study the therapeutic effect of a semisynthetic experimental diet in the pathogenesis of Crohn's disease (CD)-like inflammation in the ileum.
TNFΔARE/WT mice were fed chow and experimental diets partially fortified with gluten in a dose and time-dependent manner. Histopathology, markers of inflammation, intraepithelial lymphocytes phenotypes, and antigen-specific reactivation of CD4⁺ T cells were determined.
TNFΔARE/WT mice being transferred to an experimental diet with 7 but not with 10 or 14 weeks of age were protected from development of Crohn's disease-like ileitis. Although disease-related CD8αβ⁺ intraepithelial lymphocytes were increased irrespective of dietary intervention, the protective effect of experimental diet was associated with decreased expression of inflammation markers in ileal tissues. In addition, CD4⁺ T-cell reactivation in bacterial antigen-primed dendritic cell cocultures was not altered between semisynthetic and chow diet-fed TNFΔARE/WT mice, suggesting bacteria-independent mechanisms. Most importantly, gluten-fortified experimental diet induced chronic ileitis in TNFΔARE/WT mice, despite the fact that gluten-derived peptides failed to induce CD4⁺ T-cell activation. Reduced occludin expression levels suggest a negative role of gluten-fortified experimental diet on intestinal barrier integrity.
Crohn's disease-like ileitis can be prevented at early stages of disease development using a semisynthetic experimental diet. Gluten was identified as antigen-independent dietary factor relevant for the induction of chronic inflammation in the small intestine of TNFΔARE/WT mice.
肠内营养用于治疗炎症性肠病的一部分患者。由于饮食因素可能导致疾病易感宿主对肠道微生物群产生强烈的免疫反应，我们使用 TNFΔARE/WT 小鼠来研究半合成实验饮食在回肠炎样炎症发病机制中的治疗作用克罗恩病（CD）。
TNFΔARE/WT 小鼠以剂量和时间依赖性方式用谷朊粉部分强化的常规饮食和实验饮食喂养。测定组织病理学、炎症标志物、上皮内淋巴细胞表型和 CD4+T 细胞的抗原特异性再激活。
14 周龄而非 7 周龄的 TNFΔARE/WT 小鼠转至实验饮食可预防出现 CD 样回肠炎。尽管无论饮食干预与否，与疾病相关的 CD8αβ+上皮内淋巴细胞均增加，但实验饮食的保护作用与回肠组织中炎症标志物表达降低有关。此外，在细菌抗原刺激的树突状细胞共培养物中，半合成饮食和常规饮食喂养的 TNFΔARE/WT 小鼠之间的 CD4+T 细胞再激活没有改变，提示存在细菌非依赖性机制。最重要的是，尽管谷朊粉衍生肽未能诱导 CD4+T 细胞活化，但强化谷朊粉的实验饮食仍会诱导 TNFΔARE/WT 小鼠发生慢性回肠炎。紧密连接蛋白表达水平降低提示强化谷朊粉的实验饮食对肠道屏障完整性有负面影响。
使用半合成实验饮食可以在疾病发展的早期预防出现 CD 样回肠炎。谷朊粉被鉴定为与 TNFΔARE/WT 小鼠小肠慢性炎症诱导相关的抗原非依赖性饮食因素。
