IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Gastroenterology. 2024 Nov;167(6):1152-1166. doi: 10.1053/j.gastro.2024.07.004. Epub 2024 Jul 14.
BACKGROUND & AIMS: The pathophysiology of irritable bowel syndrome (IBS) is multifactorial and includes epithelial barrier dysfunction, a key element at the interface between the gut lumen and the deeper intestinal layers. Beneath the epithelial barrier there is the vascular one representing the last barrier to avoid luminal antigen dissemination The aims of this study were to correlate morpho-functional aspects of epithelial and vascular barriers with symptom perception in IBS.
Seventy-eight healthy subjects (controls) and 223 patients with IBS were enrolled in the study and phenotyped according to validated questionnaires. Sugar test was used to evaluate in vivo permeability. Immunohistochemistry, western blot, and electron microscopy were used to characterize the vascular barrier. Vascular permeability was evaluated by assessing the mucosal expression of plasmalemma vesicle-associated protein-1 and vascular endothelial cadherin. Caco-2 or human umbilical vein endothelial cell monolayers were incubated with soluble mediators released by mucosal biopsies to highlight the mechanisms involved in permeability alteration. Correlation analyses have been performed among experimental and clinical data.
The intestinal epithelial barrier was compromised in patients with IBS throughout the gastrointestinal tract. IBS-soluble mediators increased Caco-2 permeability via a downregulation of tight junction gene expression. Blood vessel density and vascular permeability were increased in the IBS colonic mucosa. IBS mucosal mediators increased permeability in human umbilical vein endothelial cell monolayers through the activation of protease-activated receptor-2 and histone deacetylase 11, resulting in vascular endothelial cadherin downregulation. Permeability changes correlated with intestinal and behavioral symptoms and health-related quality of life of patients with IBS.
Epithelial and vascular barriers are compromised in patients with IBS and contribute to clinical manifestations.
肠易激综合征（IBS）的病理生理学是多因素的，包括上皮屏障功能障碍，这是肠腔和更深层肠层之间界面的关键要素。在上皮屏障之下是血管屏障，它是防止腔内容物传播的最后一道屏障。本研究的目的是将上皮和血管屏障的形态功能方面与 IBS 的症状感知相关联。
本研究纳入了 78 名健康受试者（对照组）和 223 名 IBS 患者，并根据经过验证的问卷进行了表型分析。糖试验用于评估体内通透性。免疫组织化学、western blot 和电子显微镜用于表征血管屏障。通过评估黏膜质膜囊泡相关蛋白-1 和血管内皮钙黏蛋白的表达来评估血管通透性。将黏膜活检释放的可溶性介质孵育在 Caco-2 或人脐静脉内皮细胞单层上，以突出参与通透性改变的机制。对实验和临床数据进行了相关性分析。
IBS 患者的整个胃肠道上皮屏障受损。IBS 可溶性介质通过下调紧密连接基因表达增加 Caco-2 的通透性。IBS 结肠黏膜的血管密度和血管通透性增加。IBS 黏膜介质通过激活蛋白酶激活受体-2 和组蛋白去乙酰化酶 11 增加人脐静脉内皮细胞单层的通透性，导致血管内皮钙黏蛋白下调。通透性变化与 IBS 患者的肠道和行为症状以及健康相关生活质量相关。
IBS 患者的上皮和血管屏障受损，并导致临床表现。
