Weintraub Y, Cohen S, Anafy A, Chapnik N, Tsameret S, Ben-Tov A, Yerushalmy-Feler A, Dotan I, Tauman R, Froy O
Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Dig Dis Sci. 2023 Jun;68(6):2454-2462. doi: 10.1007/s10620-023-07847-y. Epub 2023 Feb 6.
Changes in the expression of clock genes have been reported in inflammatory bowel disease (IBD) patients.
We aimed to investigate whether reduced inflammation restores clock gene expression to levels of healthy controls.
This was a prospective study. Participants completed questionnaires providing data on demographics, sleeping habits, and disease activity. Anthropometric parameters, C-reactive protein (CRP), and fecal calprotectin (Fcal) levels were collected. Peripheral blood samples were analyzed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1, PER2) expression. Patients with IBD were separated by diagnosis into ulcerative colitis (UC) and Crohn's disease (CD). Each diagnosis was further divided into active disease and disease under remission.
Forty-nine patients with IBD and 19 healthy controls completed the study. BMAL1 and PER2 were significantly reduced in active patients with UC compared to patients with UC in remission. BMAL1, PER1, and PER2 were significantly reduced in patients with UC with CRP > 5 mg/dl. PER2, CRY1, and CRY2 were significantly reduced in patients with UC with Fcal > 250 mg/kg. Clock gene expression of patients with UC in remission was comparable to healthy controls. When all patients with IBD were analyzed, an overshoot in CRY1 expression was observed in patients in remission, patients with CRP < 5 mg/dl, and patients with Fcal < 250 mg/kg.
CRP and Fcal are inversely related to clock gene levels in patients with UC. CRY1 may play a role in counteracting the anti-inflammatory processes when remission is induced in patients with IBD.
ClinicalTrials.gov Identifier: NCT03662646.
炎症性肠病（IBD）患者中已报道了生物钟基因表达的变化。
我们旨在研究炎症减轻是否能使生物钟基因表达恢复到健康对照水平。
这是一项前瞻性研究。参与者完成问卷调查，提供有关人口统计学、睡眠习惯和疾病活动的数据。收集人体测量参数、C反应蛋白（CRP）和粪便钙卫蛋白（Fcal）水平。分析外周血样本中生物钟基因（CLOCK、BMAL1、CRY1、CRY2、PER1、PER2）的表达。IBD患者按诊断分为溃疡性结肠炎（UC）和克罗恩病（CD）。每种诊断进一步分为活动期疾病和缓解期疾病。
49例IBD患者和19名健康对照完成了研究。与缓解期UC患者相比，活动期UC患者的BMAL1和PER2显著降低。CRP>5mg/dl的UC患者中，BMAL1、PER1和PER2显著降低。Fcal>250mg/kg的UC患者中，PER2、CRY1和CRY2显著降低。缓解期UC患者的生物钟基因表达与健康对照相当。当分析所有IBD患者时，在缓解期患者、CRP<5mg/dl的患者和Fcal<250mg/kg的患者中观察到CRY1表达的过度升高。
UC患者中，CRP和Fcal与生物钟基因水平呈负相关。CRY1可能在IBD患者诱导缓解时对抗抗炎过程中发挥作用。
ClinicalTrials.gov标识符：NCT03662646。
