心境稳定剂影响双相情感障碍躁狂发作患者肠道菌群变化  

Effect of Mood Stabilizers on Gut Microbiota in Patients with Bipolar Disorder

作　　者：尚玲 李琪 杨栋[1] 刘学军[1] 张雪花[1] SHANG Ling;LI Qi;YANG Dong;LIU Xue-jun;ZHANG Xue-hua(Department of Psychiatry,The Hunan Brain Hospital,Changsha,410007,China)

机构地区：[1]湖南省脑科医院精神科,长沙410007

出　　处：《神经损伤与功能重建》2022年第5期259-263,共5页Neural Injury and Functional Reconstruction

基　　金：湖南省重点研发计划项目(2020SK2123);湖南省中医药科研计划项目(202032);湖南省卫生计生委科研课题(C2019038,20200817);湖南省卫生健康委重点指导课题(20201050);湖南省发改委创新研发项目(25)

摘　　要：目的:探讨心境稳定剂是否通过影响肠道菌群改善双相情感障碍(BD)躁狂发作患者症状。方法:利用杨氏躁狂量表(YMRS)评估42例BD患者治疗前、后的临床症状,并采集粪便样本提取基因组DNA。经PCR扩增、文库构建和质检后,利用16S rDNA高通量测序和Uparse软件聚类筛选获得OTUs;利用QIIME软件计算肠道菌群α多样性的指数(Chao1指数、Observed species指数、Shannon指数和Simpson指数);使用基于OTUs的Bray-Curtis距离进行PCoA分析,计算肠道菌群β多样性;利用LEfSe软件应用线性判别分析方法(LDA)进行差异物种筛选;ELISA检测BD患者治疗前、后血清IL-1β和TNF-α含量。结果:治疗前BD组的Chao1指数、Observed species指数、Shannon指数和Simpson指数低于HC组(P<0.05),治疗后BD组的Chao1指数和Observed species指数高于治疗前(P<0.05);治疗前BD组的厚壁菌门及其下的梭菌纲、梭菌目、瘤胃球菌科、韦荣菌科、变形菌门和放线菌门丰度高于HC组,而治疗后BD组的厚壁菌门及其下毛螺菌科、醋酸菌科和拟杆菌目的丰度高于治疗前BD组(P<0.05);治疗前BD组的毛螺菌科相对丰度低于HC组和治疗后BD组(P<0.05),而治疗后BD组毛螺菌科相对丰度与HC组差异无统计学意义(P>0.05);肠道毛螺菌科相对丰度分别与YMRS总分、IL-1β和TNF-α含量呈负相关(P<0.05)。结论:心境稳定剂可通过影响肠道菌群改善BD患者的症状。Objective:To study whether mood stabilizers improve symptoms in bipolar disorder(BD)patients by affecting gut microbiota.Methods:The Young Manic Rating Scale(YMRS)was used to evaluate the clinical symptoms of 42 patients with BD before and after treatment,and patients’stool samples were collected for DNA extraction.After PCR amplification,library construction,and quality control,OTUs were obtained by 16S rDNA high-throughput sequencing and Uparse software clustering screening.QIIME software was used to calculate the index ofαdiversity,including the Chao1 index,observed species index,Shannon index,and Simpson index.PCoA analysis using Bray-Curtis distances based on OTUs was performed to calculateβdiversity.LEfSe software was used to screen for different species by linear discriminant analysis(LDA).Serum IL-1βand TNF-αlevels were detected by ELISA before and after treatment in BD patients.Results:The indexes of Chao1,observed species,Shannon and Simpson in the BD group were lower than those in the healthy control(HC)group(P<0.05).The indexes of Chao1 and observed species in the BD group were higher after treatment than before(P<0.05).The abundance of Firmicutes and their subordinate Clostridiales,Clostridia,Ruminococcaceae,and Veillonellaceae,Proteobacteria,and Actinobacteria in the BD group before treatment was higher than that in the HC group,while the abundance of Firmicutes and its subordinate Lachnospiraceae,Acetobacteraceae,and Bacteroidales in the BD group was higher after treatment than before(P<0.05).The relative abundance of Lachnospiraceae in the BD group before treatment was lower than that of the HC group and the BD group after treatment(P<0.05),but there was no significant difference in the relative abundance of Lachnospiraceae between the BD group after treatment and the HC group(P>0.05).The relative abundance of Lachnospiraceae was negatively correlated with YMRS score and with levels of IL-1βand TNF-α(P<0.05).Conclusion:Mood stabilizers can relieve symptoms of bipolar disorder by way of gut

关 键 词：心境稳定剂 双相情感障碍 肠道菌群 毛螺菌科 IL-1Β TNF-α 

分 类 号：R741[医药卫生—神经病学与精神病学] R749.41[医药卫生—临床医学]