Ferrari Eleonora, Monzani Romina, Saverio Valentina, Gagliardi Mara, Pańczyszyn Elżbieta, Raia Valeria, Villella Valeria Rachela, Bona Gianni, Pane Marco, Amoruso Angela, Corazzari Marco
Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy.
Center for Translational Research on Autoimmune and Allergic Disease (CAAD), University of Piemonte Orientale, 28100 Novara, Italy.
Nutrients. 2021 Apr 7;13(4):1221. doi: 10.3390/nu13041221.
Exposure to gluten, a protein present in wheat rye and barley, is the major inducer for human Celiac Disease (CD), a chronic autoimmune enteropathy. CD occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen (HLA) DQ2/DQ8. Gut epithelial cell stress and the innate immune activation are responsible for the breaking oral tolerance to gliadin, a gluten component. To date, the only treatment available for CD is a long-term gluten-free diet. Several studies have shown that an altered composition of the intestinal microbiota (dysbiosis) could play a key role in the pathogenesis of CD through the modulation of intestinal permeability and the regulation of the immune system. Here, we show that gliadin induces a chronic endoplasmic reticulum (ER) stress condition in the small intestine of a gluten-sensitive mouse model and that the coadministration of probiotics efficiently attenuates both the unfolded protein response (UPR) and gut inflammation. Moreover, the composition of probiotics formulations might differ in their activity at molecular level, especially toward the three axes of the UPR. Therefore, probiotics administration might potentially represent a new valuable strategy to treat gluten-sensitive patients, such as those affected by CD.
接触麸质(一种存在于小麦、黑麦和大麦中的蛋白质)是人类乳糜泻(CD)的主要诱因,CD是一种慢性自身免疫性肠病。全球约1%的人口患有CD,这些人具有遗传易感性,携带人类白细胞抗原(HLA)DQ2/DQ8。肠道上皮细胞应激和先天性免疫激活导致对麸质成分麦醇溶蛋白的口服耐受性破坏。迄今为止,CD唯一可用的治疗方法是长期无麸质饮食。多项研究表明,肠道微生物群组成的改变(生态失调)可能通过调节肠道通透性和免疫系统在CD的发病机制中起关键作用。在此,我们表明麦醇溶蛋白在麸质敏感小鼠模型的小肠中诱导慢性内质网(ER)应激状态,并且益生菌的共同给药有效地减轻了未折叠蛋白反应(UPR)和肠道炎症。此外,益生菌制剂的组成在分子水平上的活性可能不同,特别是对UPR的三个轴。因此,给予益生菌可能是治疗麸质敏感患者(如受CD影响的患者)的一种新的有价值的策略。