食品添加剂麦芽糊精促进内质网应激驱动的黏液耗竭并加剧肠道炎症。
The Food Additive Maltodextrin Promotes Endoplasmic Reticulum Stress-Driven Mucus Depletion and Exacerbates Intestinal Inflammation.
机构信息
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
出版信息
Cell Mol Gastroenterol Hepatol. 2019;7(2):457-473. doi: 10.1016/j.jcmgh.2018.09.002. Epub 2018 Sep 11.
BACKGROUND & AIMS: Food additives, such as emulsifiers, stabilizers, or bulking agents, are present in the Western diet and their consumption is increasing. However, little is known about their potential effects on intestinal homeostasis. In this study we examined the effect of some of these food additives on gut inflammation.
METHODS
Mice were given drinking water containing maltodextrin (MDX), propylene glycol, or animal gelatin, and then challenged with dextran sulfate sodium or indomethacin. In parallel, mice fed a MDX-enriched diet were given the endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Transcriptomic analysis, real-time polymerase chain reaction, mucin-2 expression, phosphorylated p38 mitogen-activated protein (MAP) kinase quantification, and H&E staining was performed on colonic tissues. Mucosa-associated microbiota composition was characterized by 16S ribosomal RNA sequencing. For the in vitro experiments, murine intestinal crypts and the human mucus-secreting HT29-methotrexate treated cell line were stimulated with MDX in the presence or absence of TUDCA or a p38 MAP kinase inhibitor.
RESULTS
Diets enriched in MDX, but not propylene glycol or animal gelatin, exacerbated intestinal inflammation in both models. Analysis of the mechanisms underlying the detrimental effect of MDX showed up-regulation of inositol requiring protein 1β, a sensor of ER stress, in goblet cells, and a reduction of mucin-2 expression with no significant change in mucosa-associated microbiota. Stimulation of murine intestinal crypts and HT29-methotrexate treated cell line cells with MDX induced inositol requiring protein 1β via a p38 MAP kinase-dependent mechanism. Treatment of mice with TUDCA prevented mucin-2 depletion and attenuated colitis in MDX-fed mice.
CONCLUSIONS
MDX increases ER stress in gut epithelial cells with the downstream effect of reducing mucus production and enhancing colitis susceptibility.
背景与目的
食品添加剂，如乳化剂、稳定剂或增稠剂，存在于西方饮食中，其消耗量正在增加。然而，人们对它们对肠道内稳态的潜在影响知之甚少。在这项研究中，我们研究了其中一些食品添加剂对肠道炎症的影响。
方法
给小鼠饮用含有麦芽糊精（MDX）、丙二醇或动物明胶的水，然后用葡聚糖硫酸钠或吲哚美辛进行挑战。与此同时，给喂食 MDX 丰富饮食的小鼠给予内质网（ER）应激抑制剂牛磺熊脱氧胆酸（TUDCA）。对结肠组织进行转录组分析、实时聚合酶链反应、黏蛋白-2 表达、磷酸化 p38 丝裂原活化蛋白（MAP）激酶定量和 H&E 染色。通过 16S 核糖体 RNA 测序描述黏膜相关微生物群落组成。对于体外实验，用 MDX 刺激鼠肠隐窝和人黏液分泌 HT29-甲氨蝶呤处理细胞系，同时存在或不存在 TUDCA 或 p38 MAP 激酶抑制剂。
结果
富含 MDX 的饮食，而不是丙二醇或动物明胶，加剧了两种模型中的肠道炎症。对 MDX 有害影响的机制分析表明，杯状细胞中内质网应激传感器肌醇需求蛋白 1β上调，黏蛋白-2 表达减少，而黏膜相关微生物群无明显变化。用 MDX 刺激鼠肠隐窝和 HT29-甲氨蝶呤处理细胞系，通过 p38 MAP 激酶依赖性机制诱导肌醇需求蛋白 1β。用 TUDCA 治疗小鼠可防止黏蛋白-2 耗竭并减轻 MDX 喂养小鼠的结肠炎。
结论
MDX 增加了肠道上皮细胞中的内质网应激，其下游效应是减少黏液产生并增强结肠炎易感性。
Zotero 插件