Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia
Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia
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DOI：
10.1136/gutjnl-2012-303857
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发表时间：
2014-02-01
期刊：
影响因子：
24.5
通讯作者：
Farre, Ricard
中科院分区：
文献类型：
--
作者：
Vanheel, Hanne;Vicario, Maria;Farre, Ricard
目的功能性消化不良（FD）是一种极为常见的功能性胃肠疾病，其病理生理机制尚不清楚。我们假设肠屏障功能受损通过诱导低度炎症参与了这种疾病的发生和持续。因此，我们的目的是评估FD患者的十二指肠粘膜完整性和低度炎症。十二指肠活检标本来自15例符合罗马III标准的FD患者和15名年龄和性别匹配的健康志愿者。在Ussing室中测量跨上皮电阻（TEER）和细胞旁通透性。通过实时PCR、蛋白质印迹和/或免疫荧光评价细胞间粘附蛋白的表达。肥大细胞，嗜酸性粒细胞和上皮内淋巴细胞的数量进行了评估，通过免疫组化。结果与FD患者显示较低的TEER和增加细胞旁通道与健康对照组相比，这是受损的粘膜完整性的指示。此外，细胞间粘附蛋白在紧密连接、粘附连接和桥粒水平的表达异常。此外，患者的特征是存在低度炎症，如粘膜肥大细胞和嗜酸性粒细胞浸润增加所证明的。几个细胞间粘附蛋白的表达水平，增加的渗透性和低度炎症的严重程度之间的显着关联被发现。结论这些研究结果挑战经典的范式，FD患者在胃肠道中没有显示出结构性变化。我们认为，肠屏障功能受损是FD的病理生理机制。因此，恢复肠道屏障完整性可能是治疗FD患者的潜在治疗靶点。
Objective Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD.Design Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry.Results Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found.Conclusions These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.