Student Research Committee, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Decision Sciences, HEC, Université de Montréal, Montreal, QC, Canada.
Lipids Health Dis. 2024 Jul 13;23(1):216. doi: 10.1186/s12944-024-02203-z.
BACKGROUND: The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients. METHODS: In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention. RESULTS: The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 0.001). CONCLUSION: Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.
背景：肠道微生物产生的短链脂肪酸丁酸参与调控炎症反应和生物钟基因，而炎症性肠病（IBD）患者的生物钟基因调节紊乱。本研究旨在探讨丁酸钠补充对活动期溃疡性结肠炎（UC）患者生物钟基因表达、炎症、睡眠和生活质量的影响。
方法：在这项随机安慰剂对照试验中，36 例活动期 UC 患者被随机分为丁酸钠（600mg/kg）或安慰剂组，干预 12 周。采用实时聚合酶链反应（qPCR）检测全血中生物钟基因（CRY1、CRY2、PER1、PER2、BMAL1 和 CLOCK）的表达。基因表达变化以与基线相比的表达倍数变化（2^-ΔΔCT）表示。采用酶联免疫吸附测定法（ELISA）检测粪便钙卫蛋白和血清高敏 C 反应蛋白（hs-CRP）水平。干预前后分别采用匹兹堡睡眠质量指数（PSQI）和炎症性肠病问卷-9（IBDQ-9）评估睡眠质量和 IBD 生活质量（QoL）。
结果：与安慰剂相比，丁酸钠补充可显著降低钙卫蛋白水平（-133.82±155.62 比 51.58±95.57，P 值<0.001）和 hs-CRP 水平（-0.36（-1.57，-0.05）比 0.48（-0.09-4.77），P 值<0.001），上调 CRY1（2.22±1.59 比 0.63±0.49，P 值<0.001）、CRY2（2.15±1.26 比 0.93±0.80，P 值=0.001）、PER1（1.86±1.77 比 0.65±0.48，P 值=0.005）和 BMAL1（1.85±0.97 比 0.86±0.63，P 值=0.003）的表达倍数。此外，丁酸钠还能改善睡眠质量（PSQI 评分：-2.94±3.50 比 1.16±3.61，P 值<0.001）和 QoL（IBDQ-9：17.00±11.36 比 -3.50±6.87，P 值<0.001）。
结论：丁酸钠可能通过降低炎症生物标志物、上调生物钟基因、改善睡眠质量和 QoL，成为活动期 UC 患者的有效辅助治疗药物。
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