摘要
目的探讨不同严重程度失眠患者肠道菌群多样性及炎症因子水平的变化及相互关系,为失眠的病理生理研究提供理论依据。方法纳入2023年3—12月河北医科大学第一医院就诊的慢性失眠患者42例(失眠组)并在本院招募年龄、性别与失眠组相匹配的健康志愿者22名(对照组)。收集受试者一般人口学资料并采用简明国际神经精神障碍访谈(Mini-international Neuropsychiatric Interview,MINI)筛查及诊断常见精神障碍,抑郁自评量表(Self-Rating Depression Scale,SDS)和焦虑自评量表(Self-Rating Anxiety Scale,SAS)评估抑郁和焦虑情绪及变化,匹兹堡睡眠质量指数(Pittsburgh Sleep Quality Index,PSQI)评估睡眠质量,失眠严重程度指数(Insomnia Severity Index,ISI)评估失眠严重程度,胃肠道症状评分量表(Gastrointestinal Symptom Rating Scale,GSRS)评估受试者过去1周胃肠道功能和症状,同时采集受试者粪便及血液样本,使用16S rRNA测序方法检测肠道菌群并分析其多样性,并利用线性判别分析(linear discriminant analysis effect size,LEfSe)和随机森林分析筛选肠道菌群组成的差异物种;应用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)测定血清中炎症相关因子水平;将菌群多样性指数及特征菌属、炎症因子等指标与失眠症状进行Spearman相关分析,采用多元线性回归分析失眠患者疾病严重程度的影响因素。结果与对照组相比,轻度失眠组和中重度失眠组GSRS评分差异均有统计学意义(Z=-3.51、-2.72,均P<0.05)。轻度失眠组与中重度失眠组Chao1指数(Z=-3.53、-3.87)和Observed species指数(Z=-3.33、-3.74)均低于对照组(均P<0.05),中重度失眠组Shannon指数低于轻度失眠组和对照组(Z=-2.81、-2.23,均P<0.05),中重度失眠组Simpson指数也低于轻度失眠组(Z=-1.95,P=0.051)。与对照组相比,轻度失眠组与中重度失眠组β多样性指数差异均有统计学意义(F=2.96、3.12,均P<0.05);随机森林分析显示瘤胃球菌属_D和克雷伯菌属是区分轻度与中重度失眠患者的特征微生物。轻度失眠组与中重度失眠组的炎症因子水平均高于对照组。失眠患者PSQI评分与Shannon指数、Observed species指数、瘤胃球菌属_D的丰富程度呈负相关(r=-0.34、-0.30、-0.25,均P<0.05)。多元线性回归分析显示IL-1β(β=0.339,95%CI=0.014~0.716,P=0.042)与瘤胃球菌属_D(β=-0.309,95%CI=-194.591~-8.318,P=0.034)是失眠严重程度的影响因素。结论炎症水平较高、肠道菌群丰富程度低可能与更严重的失眠症状存在密切相关。同时,瘤胃球菌属_D与IL-1β可能是影响失眠患者疾病严重程度的重要因素。
Objective To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia,and to explore their interrelationships,in order to provide a theoretical basis for understanding the pathophysiology of insomnia.MethodsA total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group,and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group.General demographic data were collected,and Mini-International Neuropsychiatric Interview(MINI)was used to screen for comorbid psychiatric disorders.The Self-Rating Depression Scale(SDS)and the Self-Rating Anxiety Scale(SAS)were employed to evaluate individual′s depressive and anxiety symptoms.Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index(PSQI)and the Insomnia Severity Index(ISI),Participants′gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale(GSRS).Fecal and blood samples were collected from all participants.Gut microbiota diversity was analyzed using 16S rRNA sequencing.Differential taxa were identified using linear discriminant analysis effect size(LEfSe)and random forest analysis.Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay(ELISA).Spearman correlation analysis was used to explore the relationships between insomnia symptoms,microbial diversity indices,key microbial taxa,and inflammatory markers.Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.ResultsCompared to the control group,both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores(Z=-3.51,-2.72,both P<0.05).The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls(Z=-3.53,-3.87,both P<0.05).Similarly,the Observed species index was lower in both the mild and moderate-to-severe groups(Z=-3.33,-3.74,both P<0.05).The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls(Z=-2.81,-2.23,both P<0.05).The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group(Z=-1.95,P=0.051).Beta diversity differed significantly among the mild insomnia group,the moderate-to-severe insomnia group(P<0.05),and the control group(F=2.96,3.12,both P<0.05).Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia.Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls(P<0.05).PSQI scores were negatively correlated with the Shannon index,the Observed species index,and the relative abundance of Ruminococcus_D(r=-0.34,-0.30,and-0.25,respectively;all P<0.05).Multiple linear regression revealed that serum IL-1β(β=0.339,95%CI=0.014-0.716,P=0.042)and Ruminococcus_D(β=-0.309,95%CI=-194.591--8.318,P=0.034)were independent predictors of insomnia severity.ConclusionElevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity.Additionally,Ruminococcus_D and IL-1βmay be important factors contributing to the severity of insomnia in affected individuals.
作者
吕昭岩
白尚武
王哲
谢婷婷
于梦媛
孙亚麒
吴婷婷
高臻
王育梅
Lyu Zhaoyan;Bai Shangwu;Wang Zhe;Xie Tingting;Yu Mengyuan;Sun Yaqi;Wu Tingting;Gao Zhen;Wang Yumei(Mental Health Center,Hebei Medical University,Institute of Mental Health,Hebei Medical University,Hebei Brain Ageing and Cognitive Neuroscience Laboratory,Shijiazhuang 050031,China;Taizhou Fifth People′s Hospital,Taizhou 225300,China;Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China;Shandong Institute of Brain Science and Brain-inspired Research,Shandong First Medical University,Shandong Academy of Medical Sciences,Jinan 250117,China;Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder,Chinese Academy of Medical Sciences,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China)
出处
《中华精神科杂志》
北大核心
2025年第8期620-629,共10页
Chinese Journal of Psychiatry
基金
科技创新2030重大项目(2021ZD0200700)
河北省重点研发计划项目(21377712D)
河北省卫健委青年科技课题(20240394)。
关键词
入睡和睡眠障碍
肠道菌群
炎症因子
16S
rRNA测序
Sleep initiation and maintenance disorders
Gut microbiota
Inflammatory factors
16S rRNA sequencing
