Chair of Nutrition and Immunology, Technische Universität München, Freising-Weihenstephan, Germany ; Biofunctionality Unit, ZIEL - Research Center for Nutrition and Food Sciences, Technische Universität München, Freising-Weihenstephan, Germany.
PLoS One. 2013 Aug 16;8(8):e71661. doi: 10.1371/journal.pone.0071661. eCollection 2013.
Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD) and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn's disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD) impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn's disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn's disease-like ileitis.
TNF(ΔARE/WT) mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics) were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG) translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors.
HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNF(ΔARE/WT). Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria.
HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn's disease-relevant mouse model through mechanisms that involve increased intestinal permeability and altered luminal factors, leading to enhanced dendritic cell recruitment and promoted Th17 immune responses.
肥胖与炎症性肠病（IBD）的更严重疾病过程有关，流行病学数据确定脂肪而不是肥胖是 IBD 发展的危险因素。克罗恩病是两种主要的 IBD 表型之一，主要影响末端回肠。尽管最近的观察表明高脂肪饮食（HFD）会损害肠道屏障功能，并促使与结肠慢性炎症相关的共生菌选择，但 HFD 在克罗恩病发病机制中的作用机制尚不清楚。本研究旨在描述 HFD 对类似于克罗恩病的回肠炎的小鼠模型中慢性回肠炎症发展的影响。
与对照饮食相比，TNF(ΔARE/WT) 小鼠和野生型 C57BL/6 同窝仔鼠分别用 HFD 喂养不同时间。评估肠道病理学和代谢参数（葡萄糖耐量、肠系膜组织特征）。通过包括聚乙二醇（PEG）易位、门静脉血浆内毒素和屏障功能的细胞标志物在内的不同水平来表征肠道屏障完整性。测定上皮细胞的炎症激活以及免疫细胞向回肠组织的浸润，并与腔内因子相关联。
HFD 加重了回肠炎症，但在 TNF(ΔARE/WT) 中未引起明显的超重或典型的代谢紊乱。HFD 小鼠的回肠上皮中紧密连接蛋白 Occludin 的表达明显降低，而内毒素易位增加。上皮细胞表现出炎症相关激活标志物的增强表达，同时伴随着腔内因子驱动的树突状细胞募集和 Th17 偏向性淋巴细胞浸润到固有层。
HFD 喂养，独立于肥胖，通过增加肠道通透性和改变腔内因子的机制，加速了与克罗恩病相关的小鼠模型中小肠炎症的发病，导致树突状细胞募集增加和促进 Th17 免疫反应。
