水解酪蛋白肽通过调节肠道菌群改善睡眠质量的随机双盲安慰剂对照临床试验

Hydrolyzed casein peptides improve sleep quality by remodeling gut microbiota and activating tryptophan-melatonin pathway:a randomized,double-blind,placebo-controlled clinical trial

目的 本研究以安慰剂(片剂载体)作为对照,评价低(500 mg/d)、高剂量(1 000 mg/d)水解酪蛋白肽(HCP-2hvy)改善失眠患者睡眠质量的效果并从肠道菌群的角度分析其作用机制。方法 采用随机双盲安慰剂对照临床试验方法,纳入82名患者,分为低、高剂量组和安慰剂组。患者每日服用HCP-2hvy或安慰剂1次,疗程为14 d。收集患者治疗前后睡眠日记与睡眠监测仪数据,同时于治疗前后采集患者血液与粪便样本进行检测。结果 与安慰剂组比较,低、高剂量HCP-2hvy均能显著延长患者客观睡眠总时间(低剂量组t=2.870,P=0.005;高剂量组t=2.590,P=0.010)。高剂量HCP-2hvy能显著增加患者肠道菌群Shannon指数(t=2.716,P=0.008),同时低、高剂量HCP-2hvy均能显著增加患者肠道菌群Simpson指数(低剂量组t=2.066,P=0.041;高剂量组t=3.221,P=0.002),且低、高剂量组患者肠道菌群的CPCoA均与安慰剂组显著分离(P=0.048)。低、高剂量HCP-2hvy能分别提高肠道Faecalibacterium_prausnitzii(t=2.146, P=0.036)、Romboutsia_timonensis(t=2.263,P=0.027)的相对丰度。结论 HCP-2hvy可能通过调节肠道菌群改善失眠人群的睡眠质量。因此HCP-2hvy可以作为一种改善失眠的膳食补充剂加以推广应用。

Objective To evaluated the effect of low-(500 mg/d)and high-dose(1000 mg/d)of hydrolyzed casein peptide(HCP-2hvy)in improvement of the sleep quality of patients with insomnia and analyze the mechanism of action in terms of intestinal microbiota,using placebo(tablet vehicle)as the control.Methods A randomized,double-blind,placebo-controlled clinical trial was conducted,in which 82 patients were divided into the low-dose,high-dose and placebo group respectively.HCP-2hvy or placebo was administered qd for 14 days.Sleep diaries and sleep monitoring data as well as blood and fecal samples were collected and analyzed before and after the treatment.Results Both low-and high-dose HCP-2hvy significantly prolonged the total objective sleep time of the patients compared to the placebo group(t=2.870,P=0.005 in the low-dose group and t=2.590,P=0.010 in the high-dose group).High-dose HCP-2hvy significantly increased the Shannon index of gut microbiota(t=2.716,P=0.008);both the low-and high-dose groups significantly increased the Simpson index(t=2.066,P=0.041 in the low-dose group,and t=3.221,P=0.002 in the high-dose group),and both groups showed a CPCoA of the microbiota(P=0.048)significantly separated from that in the placebo group.Low-and high-dose of HCP-2hvy increased the relative abundances of intestinal Faecalibacterium_prausnitzii(t=2.146,P=0.036)and Romboutsia_timonensis(t=2.263,P=0.027),respectively.Conclusion HCP-2hvy may improve sleep quality in insomniacs by regulating intestinal microbiota,Which may therefore be promoted as a dietary supplement to improve insomnia.