Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy.
Cells. 2023 Mar 7;12(6):823. doi: 10.3390/cells12060823.
Celiac disease (CD) is a common systemic disorder that results from an abnormal response of human immunity to gluten intake, affecting the small intestine. In individuals who carry a genetic susceptibility, CD is triggered by environmental factors, including viral infections and dysbiosis of the gut microbiota. The gut microbiome is essential in controlling the immune system, and recent findings indicate that changes in the gut microbiome may contribute to various chronic immune disorders, such as CD through mechanisms that still require further exploration. Some bacteria exhibit epitopes that mimic gliadin and may enhance an immune response in the host. Other bacteria, including , may work in conjunction with gluten to trigger and escalate intestinal inflammation. The microbiota may also directly influence antigen development through the production of immunogenic or tolerogenic gluten peptides or directly influence intestinal permeability through the release of zonulin. Finally, the gut microbiome can impact intestinal inflammation by generating proinflammatory or anti-inflammatory cytokines and metabolites. It is crucial to consider the impact of genetic factors (specifically, HLA-DQ haplotypes), perinatal elements such as birth mode, type of infant feeding, and antibiotic and infection exposure on the composition of the early intestinal microbiome. According to the available studies, the gut microbiome alterations associated with CD tend to exhibit a decreased presence of beneficial bacteria, including some anti-inflammatory species. However, some controversy remains as some reports have found no significant differences between the gut microbiomes of individuals with and without CD. A better understanding of the gut microbiome's role in the development of CD would greatly benefit both prevention and treatment efforts, especially in complicated or treatment-resistant cases. Here, we have attempted to summarize the available evidence on the relationship between the gut microbiota and CD, with a particular focus on potential therapeutic targets.
乳糜泻(CD)是一种常见的全身性疾病,由人类对麸质摄入的异常免疫反应引起,主要影响小肠。在携带遗传易感性的个体中,CD 由环境因素触发,包括病毒感染和肠道微生物群落失调。肠道微生物群落对于控制免疫系统至关重要,最近的研究结果表明,肠道微生物群落的变化可能通过仍需进一步探索的机制导致各种慢性免疫疾病,如 CD。一些细菌表现出与麦胶蛋白类似的表位,可能增强宿主的免疫反应。其他细菌,包括 ,可能与麸质协同作用,引发并加剧肠道炎症。微生物群落还可以通过产生免疫原性或耐受性的麸质肽直接影响抗原发育,或通过释放 zonulin 直接影响肠道通透性。最后,肠道微生物群落可以通过产生促炎或抗炎细胞因子和代谢物来影响肠道炎症。考虑遗传因素(特别是 HLA-DQ 单倍型)、围产期因素(如分娩方式、婴儿喂养类型以及抗生素和感染暴露)对早期肠道微生物群落组成的影响至关重要。根据现有研究,与 CD 相关的肠道微生物群落变化往往表现出有益细菌(包括一些抗炎 物种)存在减少。然而,一些争议仍然存在,因为一些报告发现 CD 患者和无 CD 患者的肠道微生物群落之间没有显著差异。更好地了解肠道微生物群在 CD 发展中的作用将极大地有益于预防和治疗工作,特别是在复杂或治疗抵抗的情况下。在这里,我们试图总结肠道微生物群与 CD 之间关系的现有证据,特别关注潜在的治疗靶点。