精神分裂症患者肠道菌群多态性与代谢产物的关系

Association between gut microbiota polymorphisms and metabolites in patients with schizophrenia

目的 探讨精神分裂症患者与体检健康者的肠道菌群结构及其代谢产物的差异。方法 采用16S rRNA测序技术对21例精神分裂症患者和21例体检健康者的粪便标本的肠道菌群进行测序,并采用液相色谱-质谱(LC-MC)非靶向代谢组学检测精神分裂症患者和体检健康者中17例粪便标本肠道菌群的代谢产物。通过不同的分析方法和建模筛选精神分裂症患者属水平上的特征性微生物及其代谢产物。结果 16S rRNA测序分析结果显示,属水平上精神分裂症患者肠道菌群中有19个菌属相对丰度存在差异(P<0.05),其中上调菌属有12个:安德克菌属、消化链球菌属、梭菌属、肠球菌属、锥形杆菌属、普雷沃菌属、梭杆菌属、醋酸杆菌属、疣微菌属、瘤胃球菌属、丁酸弧菌属、优杆菌属;下调的菌属有7个:粪杆菌属、嗜血菌属、毛螺旋菌属、德克斯菌属、假丁酸弧菌属、SMB53、氨基酸球菌属。在代谢组学实验结果可见7个代谢物存在明显差异,其中异丙肾上腺素、R-3-羟基肉豆蔻酸、十一酸、鹅去氧胆酸、邻氨基苯甲酸上调,而13-二甲基尿酸、137-三甲基尿酸下调(P<0.05)。属水平微生物差异物种与差异代谢物之间的相互关系热图结果显示,特征微生物和特征代谢物存在一定的关联性。结论 该研究发现精神分裂症患者较体检健康者的肠道菌群结构及其代谢产物有明显的差异性。

Objective To investigate the differences in gut microbiota structure and metabolites between patients with schizophrenia and healthy individuals.Methods 16S rRNA sequencing technology was used to sequence the intestinal flora of stool samples from 21 schizophrenia patients and 21 healthy individuals.Liquid chromatography-mass spectrometry(LC-MC)non-targeted metabolomics was used to detect the metabolites of intestinal flora in 17 stool samples from schizophrenia patients and healthy individuals.Characteristic microorganisms and their metabolites at the genus level in schizophrenia patients were screened by different analytical methods and modeling.Results 16S rRNA sequencing analysis showed that there were differences in the relative abundance of 19 genera in the intestinal flora of patients with schizophrenia at the genus level(P<0.05),of which 12 genera were up-regulated:Anderella,Peptostreptococcus,Clostridium,Enterococcus,Conebacterium,Prevotella,Fusobacterium,Acetobacter,Verrucobacterium,Ruminococcus,Butyric Vibrio,Eubacterium.A total of 7 genera were down-regulated:Faecalibacterium,Haemophilus,Lachnospira,Dexterus,Pseudobutyric Vibrio,SMB53,and Aminococcus.There were significant differences in 7 metabolites in the results of metabolomics experiments.Among them,isoproterenol,R-3-hydroxymyristic acid,undecanoic acid,chenodeoxycholic acid,and anthranilic acid were up-regulated,while 13-Dimethyluric acid and 137-trimethyluric acid were down-regulated(P<0.05).The heat map results of the relationship between the differential species and differential metabolites of microorganisms at the genus level showed that there was a certain correlation between characteristic microorganisms and characteristic metabolites.Conclusion This study found that there were significant differences in the gut microbiota structure and metabolites between schizophrenia patients and healthy individuals.