关键词: Crohn’s disease dysbiosis immunoglobulin A inflammatory bowel disease microbiome ulcerative colitis

Mesh : Adult Bacteria / growth & development immunology Clostridiales / growth & development immunology Cohort Studies Colitis, Ulcerative / drug therapy immunology microbiology physiopathology Crohn Disease / drug therapy immunology microbiology physiopathology Disease Progression Female Gastrointestinal Microbiome / immunology physiology Humans Immunoglobulin A, Secretory / immunology Inflammatory Bowel Diseases / drug therapy immunology microbiology physiopathology Male Tumor Necrosis Factor-alpha / antagonists & inhibitors

来  源:   DOI:10.1016/j.chom.2020.12.003   PDF(Pubmed)

Abstract:
The immunopathogenesis of inflammatory bowel disease (IBD) has been attributed to a combination of host genetics and intestinal dysbiosis. Previous work in a small cohort of IBD patients suggested that pro-inflammatory bacterial taxa are highly coated with secretory immunoglobulin IgA. Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), we profiled IgA coating of intestinal microbiota in a large cohort of IBD patients and identified bacteria associated with disease and treatment. Forty-three bacterial taxa displayed significantly higher IgA coating in IBD compared with controls, including 8 taxa exhibiting differential IgA coating but similar relative abundance. Patients treated with anti-TNF-α therapies exhibited dramatically altered microbiota-specific IgA responses compared with controls. Furthermore, increased IgA coating of Oscillospira was associated with a delay in time to surgery. These results demonstrate that investigating IgA responses to microbiota can uncover potential disease-modifying taxa and reveal improved biomarkers of clinical course in IBD.
摘要:
炎症性肠病(IBD)的免疫发病机制归因于宿主遗传学和肠道菌群失调的结合。先前在一小部分IBD患者中的研究表明,促炎细菌分类群高度包被有分泌性免疫球蛋白IgA。使用细菌荧光激活细胞分选与16SrRNA基因测序(IgA-SEQ),我们在大量IBD患者中对肠道菌群的IgA涂层进行了分析,并确定了与疾病和治疗相关的细菌.与对照组相比,43个细菌类群在IBD中显示出明显更高的IgA涂层,包括8个分类单元,表现出不同的IgA涂层,但相对丰度相似。与对照组相比,用抗TNF-α治疗的患者表现出显著改变的微生物群特异性IgA反应。此外,舌尖IgA涂层的增加与手术时间的延迟有关.这些结果表明,研究IgA对微生物群的反应可以揭示潜在的疾病修饰类群,并揭示IBD临床过程中改善的生物标志物。
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