Increased Ileal Immunoglobulin A Production and Immunoglobulin A-Coated Bacteria in Diarrhea-Predominant Irritable Bowel Syndrome
Increased Ileal Immunoglobulin A Production and Immunoglobulin A-Coated Bacteria in Diarrhea-Predominant Irritable Bowel Syndrome
复制标题
腹泻型肠易激综合征中回肠免疫球蛋白 A 的产生和免疫球蛋白 A 包被的细菌增加
DOI：
10.14309/ctg.0000000000000146
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发表时间：
2020-03-01
影响因子：
3.6
通讯作者：
Li, Yanqing
中科院分区：
文献类型：
--
作者：
Liu, Yi;Yuan, Xunyi;Li, Yanqing
结论：免疫激活和肠道微生物生态失调可诱发以大肠杆菌为主的肠易激综合征（IBS-D）。我们研究了回肠免疫球蛋白A（伊加）和IgA包被的细菌在IBS-D发病机制中的作用。方法：收集32名健康志愿者和44名IBS-D患者的外周血、粪便样本以及回肠和盲肠活检。定量逆转录聚合酶链反应用于评估差异基因表达。伊加水平的血液和粪便样品进行定量的酶联免疫吸附试验。通过免疫荧光成像评估伊加+细胞。使用基于流式细胞术的伊加+细菌细胞分选和16 S rRNA基因测序（IgA-SEQ）来分离和鉴定粪便伊加+细菌。结果：IBS-D患者粪便伊加，特别是IgA 1，表达上调。伊加类转换和B细胞活化因子受体在患者回肠末端增加。与对照组相比，患者的肠道微生物群组成发生了变化。IgA-SEQ显示IBS-D患者粪便中IgA包被细菌的比例显著增加。IBS-D患者的伊加+细菌与健康对照组和IBS-D患者的伊加−细菌相比，表现出更高的土方志贺菌、颗粒菌和嗜血杆菌丰度。土衣志贺菌伊加包被指数与焦虑、抑郁呈正相关。肠溶志贺菌相对丰度、管腔伊加活性和一些IgA包被细菌的改变与IBS-D的临床表现呈正相关。讨论内容：微生物生态失调可能促进末端回肠粘膜产生更高水平的伊加，通过激活伊加类别转换增加IgA包被细菌的比例，这可能调节IBS-D的局部炎症和临床表现。伊加可能介导微生物生态失调对IBS-D发病机制的影响。
OBJECTIVES: Immune activation and intestinal microbial dysbiosis could induce diarrhea-predominant irritable bowel syndrome (IBS-D). We examined the roles of ileal immunoglobulin A (IgA) and IgA-coated bacteria in IBS-D pathogenesis. METHODS: Peripheral blood, fecal samples, and ileal and cecal biopsies were collected from 32 healthy volunteers and 44 patients with IBS-D. Quantitative reverse transcriptase polymerase chain reaction was used to assess differential gene expression. IgA levels in the blood and fecal samples were quantified by an enzyme-linked immunosorbent assay. IgA+ cells were assessed by immunofluorescence imaging. Flow-cytometry-based IgA+ bacterial cell sorting and 16S rRNA gene sequencing (IgA-SEQ) was used to isolate and identify fecal IgA+ bacteria. RESULTS: Fecal IgA, particularly IgA1, was upregulated in patients with IBS-D. IgA class switch and B cell–activating factor-receptor were increased in the terminal ileum of patients. The intestinal microbiota composition was altered in patients compared with that in controls. IgA-SEQ showed that the proportion of fecal IgA-coated bacteria was increased significantly in patients with IBS-D. IgA+ bacteria in patients with IBS-D showed higher abundances of Escherichia–Shigella, Granulicatella, and Haemophilus compared with healthy controls and IgA− bacteria in patients with IBS-D. The Escherichia–Shigella IgA coating index was positively correlated with anxiety and depression. The Escherichia–Shigella relative abundance, luminal IgA activity, and some altered IgA-coated bacteria were positively associated with the clinical manifestations of IBS-D. DISCUSSION: Microbial dysbiosis may promote the terminal ileal mucosa to produce higher levels of IgA, increasing the proportion of IgA-coated bacteria by activating IgA class switching, which might regulate local inflammation and clinical manifestations in IBS-D. IgA may mediate the effects of microbial dysbiosis on the pathogenesis of IBS-D.