Mauduit Arthur, Mas Emmanuel, Solà-Tapias Nuria, Ménard Sandrine, Barreau Frédérick
INSERM UMR 1220, INRAE UMR 1416, ENVT, Université de Toulouse Paul Sabatier, 31000, Toulouse, France.
Service de Gastroentérologie, Hépatologie, Nutrition, Diabétologie Et Maladies Héréditaires du Métabolisme, Hôpital Des Enfants, CHU de Toulouse, 31300, Toulouse, France.
J Gastroenterol. 2025 Aug 21. doi: 10.1007/s00535-025-02289-x.
Crohn's disease (CD) and ulcerative colitis (UC), the two main subtypes of inflammatory bowel diseases (IBD), are chronic relapsing inflammatory disorders of the gastrointestinal tract. IBD are multifactorial diseases with a complex etiology, involving an intricate interaction between environmental and genetic factors. Since the discovery of NOD2 gene in 2001, genome-wide association studies have reported more than 200 IBD susceptibility loci. The strongest associations highlighted five main pathways as altered in IBD: bacterial sensing (NOD2), autophagy (ATG16L1, IRGM…), endoplasmic reticulum stress (XBP1, ARG2…), Th-17 immune pathway (IL23-receptor), and the vitamin D receptors (VDR). The pathophysiology of IBD results from an abnormal immune response toward an altered gut microbiota. Although the primum movens remains unknown, an increased intestinal permeability is clearly involved in the genesis of this abnormal crosstalk, leading to whole tissue inflammation. Thus, an excessive intestinal permeability, or "leaky gut", has been described to precede the development of CD. Moreover, in IBD, intestinal permeability is described to be a sensitive prognostic indicator of relapse in patients with quiescent IBD. Thus, the aim of this review is to highlight the molecular and cellular mechanisms by which the main pathways associated with IBD could contribute to alter the intestinal permeability to favour and/or exacerbate chronic inflammation, leading to debilitating diseases.
克罗恩病（CD）和溃疡性结肠炎（UC）是炎症性肠病（IBD）的两种主要亚型，是胃肠道的慢性复发性炎症性疾病。IBD是多因素疾病，病因复杂，涉及环境和遗传因素之间的复杂相互作用。自2001年发现NOD2基因以来，全基因组关联研究已报告了200多个IBD易感位点。最强的关联突出了IBD中改变的五个主要途径：细菌感应（NOD2）、自噬（ATG16L1、IRGM…）、内质网应激（XBP1、ARG2…）、Th-17免疫途径（IL23受体）和维生素D受体（VDR）。IBD的病理生理学源于对改变的肠道微生物群的异常免疫反应。虽然原动力尚不清楚，但肠道通透性增加显然参与了这种异常串扰的发生，导致全组织炎症。因此，有人描述在CD发生之前肠道通透性就已经过高，即“肠漏”。此外，在IBD中，肠道通透性被认为是静止期IBD患者复发的敏感预后指标。因此，本综述的目的是强调与IBD相关的主要途径可能通过哪些分子和细胞机制改变肠道通透性，从而促进和/或加剧慢性炎症，导致使人衰弱的疾病。
