Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction
Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction
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DOI：
10.1136/gutjnl-2015-310523
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发表时间：
2016-05-01
期刊：
影响因子：
24.5
通讯作者：
Verhasselt, Valerie
中科院分区：
文献类型：
--
作者：
Tulic, Meri K.;Vivinus-Nebot, Mylene;Verhasselt, Valerie
背景肠道屏障功能异常是肠道炎症性疾病的基础。已知屋尘螨（HDM）空气过敏原诱导呼吸道粘膜炎症。我们最近报道过敏原屋尘螨（Dermatophagoides pteronyssinus，Der p1）存在于啮齿类动物的肠道中，目的检测Der p1是否存在于人类肠道中，并评估其对肠道屏障功能和炎症的影响。通过ELISA测量Der p1。在存在或不存在半胱氨酸蛋白酶抑制剂或丝氨酸蛋白酶抑制剂的情况下，评估HDM对肠道通透性、紧密连接和粘蛋白表达以及细胞因子产生的影响。在口服HDM或蛋白酶中和的HDM的小鼠中检查HDM的体内作用。结果HDM Der p1在人肠道中表达，在肠易激综合征（IBS）患者中HDM Der p1表达水平明显高于正常人。在健康患者的结肠活检中，HDM增加上皮通透性（p< 0.001），减少紧密连接蛋白和粘液屏障的表达。这些作用与肿瘤坏死因子（TNF）-α和白细胞介素（IL）-10的产生增加有关，并被半胱氨酸蛋白酶抑制剂消除（p< 0.01）。HDM效应不需要Th 2免疫。结果在小鼠体内得到证实。在IBS患者中，HDM进一步恶化了肠道屏障功能，诱导了TNF-α的分泌，但未能诱导IL-10的分泌（p< 0.001）。HDM可能是肠道功能障碍的重要触发因素，值得进一步研究。
Background Abnormal gut barrier function is the basis of gut inflammatory disease. It is known that house dust mite (HDM) aero-allergens induce inflammation in respiratory mucosa. We have recently reported allergen from Dermatophagoides pteronyssinus (Der p1) to be present in rodent gut.Objective To examine whether Der p1 is present in human gut and to assess its effect on gut barrier function and inflammation.Design Colonic biopsies, gut fluid, serum and stool were collected from healthy adults during endoscopy. Der p1 was measured by ELISA. Effect of HDM was assessed on gut permeability, tight-junction and mucin expression, and cytokine production, in presence or absence of cysteine protease inhibitors or serine protease inhibitors. In vivo effect of HDM was examined in mice given oral HDM or protease-neutralised HDM. Role of HDM in low-grade inflammation was studied in patients with IBS.Results HDM Der p1 was detected in the human gut. In colonic biopsies from healthy patients, HDM increased epithelial permeability (p< 0.001), reduced expression of tight-junction proteins and mucus barrier. These effects were associated with increased tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 production and were abolished by cysteine-protease inhibitor (p< 0.01). HDM effects did not require Th2 immunity. Results were confirmed in vivo in mice. In patients with IBS, HDM further deteriorated gut barrier function, induced TNF-alpha but failed to induce IL-10 secretion (p< 0.001).Conclusions HDM, a ubiquitous environmental factor, is present in the human gut where it directly affects gut function through its proteolytic activity. HDM may be an important trigger of gut dysfunction and warrants further investigation.