Dysregulation of Intestinal Microbiota Elicited by Food Allergy Induces IgA-Mediated Oral Dysbiosis
Dysregulation of Intestinal Microbiota Elicited by Food Allergy Induces IgA-Mediated Oral Dysbiosis
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DOI：
10.1128/iai.00741-19
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发表时间：
2020-01-01
影响因子：
3.1
通讯作者：
Kuwata, Hirotaka
中科院分区：
文献类型：
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作者：
Matsui, Shohei;Kataoka, Hideo;Kuwata, Hirotaka
食物过敏是对特定食物的一种危及生命的反应，肠道微生物区系失衡(生物失调)被认为是这种疾病的原因之一。同时，宿主的免疫反应在该病中也起着重要作用。值得注意的是，从受损或坏死的肠上皮细胞释放的白介素33(IL-33)有助于产生IL-2的CD4辅助T细胞(Th2)反应。然而，肠道和口腔生物失调与食物过敏之间的因果关系仍不清楚。在这项研究中，我们分析了肠道和口腔生物失调对食物过敏发展的影响。用BALB/c小鼠注射卵白蛋白(OVA)建立食物过敏模型。采用基质辅助激光解吸电离飞行时间质谱仪(MALDI-TOF MS)鉴定粪便活菌。实时定量聚合酶链式反应(Real-Time-PCR)检测粪便分离菌刺激的小鼠结肠癌细胞IL33的表达。用流式细胞仪分析小鼠的肠道T细胞。用酶联免疫吸附试验测定唾液中的IgA水平，用流式细胞仪检测口腔细菌的IgA结合率。在粪便细菌中，柠檬酸杆菌的丰度最高。在过敏小鼠的粪便中增加，并诱导结肠-26细胞中IL33的表达。口服柯萨里柠檬酸杆菌JCM1658可加重全身过敏症状，减少肠道Th17细胞。过敏小鼠唾液中IgA及与IgA结合的口腔细菌增多。根据上述结果，食物过敏导致肠道和口腔的生物失调。柠檬酸杆菌属通过诱导肠上皮细胞释放IL-33加重过敏症状。
Food allergy is a life-threatening response to specific foods, and microbiota imbalance (dysbiosis) in gut is considered a cause of this disease. Meanwhile, the host immune response also plays an important role in the disease. Notably, interleukin 33 (IL-33) released from damaged or necrotic intestinal epithelial cells facilitates IL-2-producing CD4 helper T (Th2) responses. However, causal relationships between the gut and oral dysbiosis and food allergy remain unknown. In this study, we analyzed effects of gut and oral dysbiosis on development of food allergy. A murine model of food allergy was established via ovalbumin (OVA) injection in BALB/c mice. Viable fecal bacteria were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). il33 expression in colon-26 mouse colon cells stimulated by isolated fecal bacteria was quantified by real-time PCR. Intestinal T cells from the mice were analyzed by flow cytometry. Salivary IgA levels were quantified by enzyme-linked immunosorbent assay (ELISA), and IgA-bound oral bacteria were detected by flow cytometry. Among fecal bacteria, the abundance of Citrobacter sp. increased in the feces of allergic mice and induced il33 expression in colon-26 cells. Orally administered Citrobacter koseri JCM1658 exacerbated systemic allergic symptoms and reduced intestinal Th17 cells. Salivary IgA and IgA-bound oral bacteria increased in the allergic mice. Based on the results described above, food allergy induced both gut and oral dysbiosis. Citrobacter sp. aggravated allergy symptoms by inducing IL-33 release from intestinal epithelial cells.