BACKGROUND & AIMS Sleep disruption modifies the immune system and can trigger flares of inflammatory bowel diseases (IBD). Changes in expression of clock genes have been reported in patients with IBD. We investigated whether a change in the circadian clock is an early event in development of IBD. METHODS We performed a prospective study of patients younger than 21 years old who underwent diagnostic endoscopies at the pediatric and adult gastroenterology units at the Tel Aviv Sourasky Medical Center from August 2016 through August 2017. Questionnaires were completed by 32 patients with IBD (8-21 years old) and 18 healthy individuals (controls) that provided data on demographics, sleep, disease activity scores. We also obtained data on endoscopic scores, anthropometric parameters, blood level of C-reactive protein (CRP), and fecal level of calprotectin. Peripheral blood and intestinal mucosa samples were analyzed for expression levels of clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1, and PER2). RESULTS Levels of CRP and fecal calprotectin were significantly higher in patients with IBD compared with controls (P<.05). Expression levels of clock genes (CLOCK, CRY1, CRY2, PER1, and PER2) were significantly lower in inflamed intestinal mucosa from patients compared with intestinal mucosa from controls (P<.05). Expression levels of all clock genes except for PER2, were also significantly lower in non-inflamed intestinal mucosal tissues from patients compared with controls (P<.05). Expression levels of clock genes (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) were lower in white blood cells from patients with IBD compared with controls. This reduction was greater in white blood cells from patients with ulcerative colitis than in patients with Crohn's disease. CONCLUSION Young, newly diagnosed, untreated patients with IBD have reduced expression of clock genes in inflamed and non-inflamed intestinal mucosal samples, and also in blood cells, compared with healthy individuals. Alterations in expression of clock genes might be an early event in IBD pathogenesis. ClinicalTrials.gov Identifier: NCT03662646.

中文翻译：

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时钟基因破坏是炎症性肠病的最初表现。

背景与目的睡眠障碍会改变免疫系统，并会引发炎症性肠病（IBD）发作。在IBD患者中已经报道了时钟基因表达的变化。我们调查了昼夜节律时钟的改变是否是IBD发展中的早期事件。方法我们对2016年8月至2017年8月在特拉维夫苏拉斯基医学中心的儿科和成人胃肠病学部门接受诊断性内镜检查的21岁以下患者进行了一项前瞻性研究。对32例IBD患者进行了问卷调查（8-21岁）岁的儿童）和18位健康的人（对照组），这些人提供了有关人口统计学，睡眠，疾病活动评分的数据。我们还获得了有关内窥镜评分，人体测量学参数，C反应蛋白（CRP）血液水平，和粪便中钙卫蛋白的水平。分析了外周血和肠粘膜样品中Clock基因（CLOCK，BMAL1，CRY1，CRY2，PER1和PER2）的表达水平。结果IBD患者的CRP和粪便钙卫蛋白水平明显高于对照组（P <0.05）。与对照组的肠粘膜相比，患者发炎的肠粘膜中时钟基因（CLOCK，CRY1，CRY2，PER1和PER2）的表达水平显着降低（P <.05）。与对照组相比，患者的非炎症性肠粘膜组织中除PER2外的所有时钟基因的表达水平也均显着降低（P <.05）。与对照组相比，IBD患者的白细胞中时钟基因（CLOCK，BMAL1，CRY1，CRY2，PER1和PER2）的表达水平较低。与溃疡性结肠炎患者相比，溃疡性结肠炎患者的白细胞减少更大。结论与健康个体相比，年轻，新诊断，未经治疗的IBD患者在发炎和未发炎的肠粘膜样品以及血细胞中时钟基因的表达降低。时钟基因表达的改变可能是IBD发病机制中的早期事件。ClinicalTrials.gov标识符：NCT03662646。时钟基因表达的改变可能是IBD发病机制中的早期事件。ClinicalTrials.gov标识符：NCT03662646。时钟基因表达的改变可能是IBD发病机制中的早期事件。ClinicalTrials.gov标识符：NCT03662646。