产γ-氨基丁酸的复合益生菌制品对睡眠的改善作用

Effect of compound probiotics with GABA production for sleep improvement

目的探讨由产γ-氨基丁酸(GABA)的特性菌株制得的复合益生菌制品对睡眠的改善作用。方法 将产GABA的特性菌株按照一定比例进行复配作为发酵剂,经长时发酵后得到益生菌及其代谢产物的混合物,喷雾干燥后制得复合益生菌制品。非靶标代谢组学检测复合益生菌制品中的代谢产物种类,再通过人群试验验证复合益生菌制品对睡眠的改善作用。招募患有睡眠障碍人群,设置复合益生菌制品作为试验组,同等剂量的GABA作为对照组,每组50人,干预时间为2周,通过匹斯堡睡眠指数量表(PSQI)和睡眠症状改善情况(包括入睡时间、半夜醒来次数及再次入睡情况、睡眠总时长)对受试人群进行干预前后对比。结果 经非靶标代谢组学检测复合益生菌制品的代谢产物非常丰富,除神经递质类物质GABA外,还有抗氧化物质如谷氨酰胺、脯氨酸、甜菜碱等,乙酸、丁酸盐类等短链脂肪酸及各种氨基酸、维生素类。这些成分在神经调节过程中发挥着重要的作用。人群试验经2周的干预后,试验组PSQI评分显著下降(t=6.120,P<0.000 1),第1周下降了34.6%,第2周下降了42.0%;对照组PSQI评分也显著下降(t=2.716,P<0.010 0),第1周下降了16.0%,第2周下降了22.2%。结论 综合PSQI评分和睡眠症状改善情况,都表明了复合益生菌制品的干预效果优于同等剂量的GABA。推测复合益生菌制品可能通过肠道菌群及代谢产物-肠-脑轴的互动,进而影响免疫和神经内分泌起到调节神经的作用,从而改善睡眠。

Objective To observe the effects of compound probiotics prepared from a characteristic strain with highγ-aminobutanoic acid(GABA) production for sleep improvement. Methods The strain with high yield of GABA was mixed in a certain proportion as the starter to obtain the mixture of probiotics and its metabolites through long-time fermentation. The compound probiotics were prepared by spray drying of the mixture. The metabolites in the compound probiotics were detected with non-target metabolomics method, and the improvement effect of the compound probiotics on sleep was verified through population test. Individuals with sleep disorders were enrolled and divided into compound probiotics group and GABA control group, 50 people in each group. The intervention period was 2 weeks. Pittsburgh Sleep Index Scale(PSQI) and improvement in sleep symptoms(including time to fall asleep, times of waking up and falling asleep again in the middle of the night, and total sleep duration) were compared before and after the intervention. Results The metabolites of the compound probiotics contained rich components by non-target metabonomics. Besides neurotransmitter substance GABA, there were antioxidant substances(such as glutamine, proline and betaine, etc.), acetic acid, butyrate and other short chain fatty acids, as well as various amino acids and vitamins. These components play an important role in neuroregulation. After 2 weeks of intervention, the PSQI in the probiotics group decreased significantly(t=6.120, P<0.000 1)by 34.6% in the first week and 42.0% in the second week;The PSQI in the control group also significantly decreased(t=2.716, P<0.010 0), 16.0% in the first week and 22.2% in the second week. Conclusion The overall PSQI and improvement in sleep symptoms showed that the intervention effect of compound probiotics is better than that of the same dose of GABA. It is speculated that the complex probiotics products may affect the immune system and neuroendocrine to regulate the nerves through the interaction of intestinal flora and metabolites-gut-brain axis, thus improving sleep.