Unit of Experimental Endoscopy, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
Institute of Translational Immunology, Department of Medicine I, University of Mainz, Mainz, Germany; Research Center for Immunology, University of Mainz, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Gastroenterology. 2014 Nov;147(5):1012-20.e4. doi: 10.1053/j.gastro.2014.07.046. Epub 2014 Jul 30.
BACKGROUND & AIMS: We investigated suspected food intolerances in patients with irritable bowel syndrome (IBS) using confocal laser endomicroscopy (CLE) for real-time visualization of structural/functional changes in the intestinal mucosa after food challenge. Patients with functional changes after food challenge (CLE+) were placed on personalized exclusion diets and followed up for long-term symptom relief. METHODS: Thirty-six IBS patients with suspected food intolerance and 10 patients with Barrett's esophagus (controls) without IBS symptoms were examined by CLE at University Hospital Schleswig-Holstein (Kiel, Germany). Diluted food antigens were administered directly to the duodenal mucosa through the working channel of the endoscope. Epithelial breaks, intervillous spaces, and the number of intraepithelial lymphocytes (IEL) were measured before and after the food challenge. CLE+ patients were placed on exclusion diets, given symptom score questionnaires, and followed up for 1 year; controls resumed their previous diet. RESULTS: CLE showed a real-time response to food antigens in 22 of 36 patients; no responses were observed in 14 of 36 patients (CLE-) or any of the controls. Baseline IELs were significantly higher in CLE+ than CLE- subjects (P = .004); numbers increased significantly after food challenge (P = .0008). Within 5 minutes of exposure of CLE+ patients to food antigens, IELs increased, epithelial leaks/gaps formed, and intervillous spaces widened. Epithelial leaks and intervillous spaces also increased significantly in CLE+ vs baseline (both P < .001). The concordance of IELs measured by CLE and conventional histology was 70.6%; they did not correlate (P = .89; r(2) = 0.027). Symptom scores improved more than 50% in CLE+ patients after a 4-week exclusion diet and increased to 74% at 12 months; symptoms continued in CLE- patients. CONCLUSIONS: Based on CLE analysis of IBS patients with a suspected food intolerance, exposure to candidate food antigens caused immediate breaks, increased intervillous spaces, and increased IELs in the intestinal mucosa. These changes are associated with patient responses to exclusion diets. Registered at clinicaltrials.gov (registration number: NCT01692613).
背景与目的:我们使用共聚焦激光内镜(CLE)实时观察食物挑战后肠黏膜的结构/功能变化,研究了肠易激综合征(IBS)患者的疑似食物不耐受。对食物挑战后出现功能改变的患者(CLE+)进行个体化排除饮食治疗,并进行长期症状缓解随访。
方法:在德国石勒苏益格-荷尔斯泰因大学医院(基尔),对 36 例疑似食物不耐受的 IBS 患者和 10 例无 IBS 症状的 Barrett 食管患者(对照组)进行 CLE 检查。通过内镜工作通道将稀释的食物抗原直接注入十二指肠黏膜。在食物挑战前后测量上皮破裂、细胞间空间和上皮内淋巴细胞(IEL)数量。CLE+患者进行排除饮食治疗,给予症状评分问卷,并随访 1 年;对照组恢复之前的饮食。
结果:在 36 例患者中,22 例 CLE 对食物抗原有实时反应(CLE+),14 例无反应(CLE-)或任何对照组均无反应。CLE+患者的基线 IEL 明显高于 CLE-患者(P=0.004);食物挑战后显著增加(P=0.0008)。暴露于食物抗原 5 分钟内,CLE+患者的 IEL 增加,上皮渗漏/间隙形成,细胞间空间增宽。上皮渗漏和细胞间空间在 CLE+患者与基线相比也显著增加(均 P<0.001)。CLE 与常规组织学测量的 IEL 一致性为 70.6%;两者无相关性(P=0.89;r²=0.027)。CLE+患者在 4 周排除饮食后症状评分改善超过 50%,12 个月时增加到 74%;CLE-患者的症状仍持续。
结论:根据疑似食物不耐受的 IBS 患者的 CLE 分析,暴露于候选食物抗原会导致肠黏膜立即出现破裂,增加细胞间空间,并增加 IEL。这些变化与患者对排除饮食的反应有关。在 clinicaltrials.gov 注册(注册号:NCT01692613)。
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