Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Hasbro Children's Hospital, Providence, RI 02903, USA; Alpert Medical School of Brown University, Providence, RI 02903, USA.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
Cell Host Microbe. 2021 Jan 13;29(1):83-93.e3. doi: 10.1016/j.chom.2020.12.003. Epub 2021 Jan 1.
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.
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组合。以前在一小部分 IBD 患者中的研究表明，促炎细菌类群高度被分泌型免疫球蛋白 IgA 包裹。我们使用细菌荧光激活细胞分选结合 16S rRNA 基因测序（IgA-SEQ），在一大群 IBD 患者中对肠道微生物组的 IgA 包被进行了分析，并确定了与疾病和治疗相关的细菌。与对照组相比，43 种细菌类群在 IBD 中表现出明显更高的 IgA 包被，其中 8 种细菌类群表现出不同的 IgA 包被但相对丰度相似。与对照组相比，接受抗 TNF-α 治疗的患者表现出明显改变的微生物群特异性 IgA 反应。此外，Oscillospira 的 IgA 包被增加与手术时间延迟有关。这些结果表明，研究针对微生物组的 IgA 反应可以揭示潜在的疾病修饰类群，并为 IBD 的临床病程提供更好的生物标志物。
