目的 分析昼夜节律紊乱人群的肠道菌群多样性和结构组成及其与认知的相关性.方法 将2022年8月至2024年10月在陆军军医大学第二附属医院工作的夜班人群(昼夜节律紊乱人群)和正常人群(昼夜节律正常人群)作为研究对象.收集昼夜节律紊乱人群[实验组(n=24)]和昼夜节律正常人群[对照组(n=24)]的身高、体质量、年龄、性别、BMI、蒙特利尔认知评估量表(Montreal Cognitive Assessment,MoCA)得分、简易精神状态检查表(Mini-Mental State Examination,MMSE)得分以及新鲜粪便,采用宏基因组学、Alpha多样性、Beta多样性、线性判别分析效应量(linear discriminant analysis effect size,LEFSE)方法、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析受试者肠道菌群的多样性和结构功能特征.结果 基线资料显示两组研究对象的身高、体质量、年龄、性别、BMI无统计学差异.Alpha多样性表明两组的ACE、Chao1、Shannon和Simpson指数无统计学差异,Beta多样性有统计学差异(P<0.01);实验组与对照组的肠道菌群结构明显不同.实验组普拉氏粪杆菌和阿加瑟菌直肠种的丰度较对照组减少,大肠杆菌和海豹菌的丰度较对照组增加(P<0.05).肠道菌群KEGG功能分析显示,实验组在Th17细胞分化和IL-17信号通路方面的水平较对照组上调(P<0.05),阿加瑟菌直肠种和普拉氏粪杆菌与MoCA呈正相关,阿加瑟菌直肠种和普拉氏粪杆菌与MMSE呈显著正相关(P<0.05,P<0.01).阿加瑟菌直肠种与IL-17信号通路和Th17细胞分化呈负相关.结论 昼夜节律紊乱人群与昼夜节律正常人群相比,肠道菌群结构和功能存在改变,阿加瑟菌直肠种可能参与调节IL-17信号通路和Th17细胞分化进而影响昼夜节律紊乱后认知评分的升高.
Characteristics of gut microbiota in people with circadian rhythm disruption and its correlation with cognition
Objective To analyze the diversity and composition of gut microbiota in individuals with circadian rhythm disruption and their correlation with cognition.Methods Night shift workers and regular shift workers were subjected from our hospital during August 2022 and October 2024.The participants with circadian rhythm disorders were assigned into an experimental group(n=24),and those with normal circadian rhythms were into a control group(n=24).Their height,weight,age,gender,body mass index(BMI)and fresh fecal samples were collected,and Montreal Cognitive Assessment(MoCA)and Mini-Mental State Examination(MMSE)were used to evaluate their mental status.Metagenomics,Alpha and Beta diversity analyses,Linear Discriminant Analysis Effect Size(LEfSe),and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were employed to investigate the diversity and function characteristics of gut microbiota in the participants.Results There were no statistical differences between the 2 groups in baseline data,such as height,weight,gender,age,and BMI(P>0.05).Alpha diversity analysis indicated that no statistical differences were observed in the ACE,Chao1,Shannon,or Simpson indices between the 2 groups,while beta diversity analysis revealed significant differences(P<0.01),suggesting different structure of gut microbiota between them.In the experimental group,the abundance of Faecalibacterium prausnitzii and Agathobacter rectalis was decreased,while that of Escherichia coli and Phocaeicola vulgaratus was increased,with significant differences when compared with the control group(P<0.05).Additionally,KEGG functional analysis showed that the experimental group had obviously higher expression levels in Th17 cell differentiation and the IL-17 signaling pathway than the control group(P<0.05).Agathobacter rectalis and Faecalibacterium prausnitzii were positively correlated with MoCA score and MMSE score(P<0.05,P<0.01).Agathobacter rectalis was negatively correlated with the IL-17 signaling pathway and Th17 cell differentiation.Conclusion Individuals with circadian rhythm disorders have significant changes in the structure and function of gut microbiota when compared to those with normal circadian rhythms.Agathobacter rectalis may be involved in the regulation of the IL-17 signaling pathway and differentiation of Th17 cells,thereby possibly impacting the increases of cognitive score related to circadian rhythm disorders.
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