不同运动方式干预对昼夜节律紊乱小鼠认知功能的影响——基于肠道菌群和非靶向代谢组学分析

Effects of Different Physical Exercise Interventions on the Cognitive Function in Mice with Circadian Rhythm Disorders:Based on the Gut Microbiota and Untargeted Metabolomics Analysis

目的研究不同运动方式干预对昼夜节律紊乱小鼠认知功能的影响,探讨肠道菌群及代谢与认知功能之间的相关性。方法采用轮回颠倒的光照周期暴露建立昼夜节律紊乱模型,将模型小鼠分为:安静组(DC)、中等强度持续训练(MICT)运动组(DM)和高强度间歇训练(HIIT)运动组(DH),另设对照组(CC),各组15只,经过6周运动干预后,运用HE染色观察结肠组织、Morris水迷宫检测认知功能、16S rRNA高通量测序检测肠道菌群以及LC-MS检测粪便代谢物。结果①DM组和DH组的腺体破坏程度有所减轻。②DM组和DH组平台潜伏期和初次抵达平台时间显著缩短,游泳距离减少,穿越站台次数和目标象限游泳时间百分比均显著增加。③DC组丰度较高的菌群为柔膜菌门和柔膜菌纲,DM组为瘤胃球菌科,DH组为Lutispora等。④DM组中肌酸、丁酸和甲硫氨酸等代谢物水平显著高于DC组,DH组中花生四烯酸等代谢物水平显著高于DC组。⑤肠道菌群中颤螺菌属、乳酸杆菌属与认知功能相关性显著,代谢物中姜黄素和油酸与认知功能相关性显著。结论MICT和HIIT可调节昼夜节律紊乱小鼠肠道菌群的结构和丰度,改善其认知功能,相关肠道菌群与代谢物参与运动改善昼夜节律紊乱小鼠认知功能的调节。

Objective To investigate the effect of different physical exercise interventions on the cognitive function in mice with circadian rhythm disorders,and to explore the correlation between gut microbiota and metabolism and cognitive function.Methods A circadian rhythm disorder model was established by a reversed light cycle exposure,and the model mice were divided into three groups:quiet group(DC),MICT exercise group(DM)and HIIT exercise group(DH),and another control group(CC),with 15 mice in each group.After 6 weeks of exercise intervention,the colon tissue was observed by HE staining;cognitive function was detected by Morris water maze and 16S rRNA high-throughput sequencing for detection of gut microbiota and LC-MS to detect fecal metabolites.Results①The degree of glandular destruction was reduced in the DM and DH groups.②Platform latency and initial arrival time at the platform were significantly shorter,swimming distance was reduced,and the number of crossing stations and percentage of swimming time in the target quadrant were significantly increased in the DM and DH groups.③The groups with higher abundance in the DC group were the phylum Tenericutes and Mollicutes;the DM group was the family Ruminococcaceae;the DH group was the genus Lutispora,etc.④Metabolite levels of creatine,butyric acid and methionine were significantly higher in the DM group than in the DC group,and metabolite levels of arachidonic acid were significantly higher in the DH group than in the DC group.⑤The correlation between Treponema spp.and Lactobacillus spp.in the intestinal flora and cognitive function was significant,so was the correlation between curcumin and oleic acid in metabolites and cognitive function.Conclusion MICT and HIIT modulate the structure and abundance of intestinal flora and improve cognitive function in mice with circadian rhythm disorders;related gut microbiota and metabolites are involved in the regulation of exercise to improve cognitive function in mice with circadian rhythm disorders.