基于高通量测序的精神分裂症患者肠道菌群多样性

Gut microbial profile analysis by high-throughput sequencing in schizophrenia patients

目的探讨精神分裂症患者肠道菌群多样性变化。方法收集16例精神分裂症患者(schizophrenia,Sch)与18例健康者(healthy donor,HD)的粪便样本,提取肠道菌群基因组,扩增16SrRNA基因,运用Illumina平台进行测序。对测序结果进行多样性和物种组成差异分析。结果精神分裂症患者组肠道菌群在门、纲、目、科、属、种、分类操作单元(operational taxonomic units,OTUs)水平的群落种类数目少于健康对照组。Alpha多样性指标中患者组的Ace指数(226.58±31.67)、Chao1指数(222.29±34.45)和Shannon指数(2.66±0.69)明显低于健康对照组(293.63±56.07、302.2±57.99、3.59±0.36),差异均有统计学意义(Ps<0.001),而Simpson指数(0.20±0.17)明显高于健康对照组(0.07±0.03),差异有统计学意义(P<0.01);Beta多样性分析显示两组研究对象肠道菌群样本可被鉴别区分。精神分裂症患者组与健康对照组样本在门和属水平上肠道菌群组成和含量有差异,其中患者组拟杆菌门和软壁菌门占比明显低于健康组,差异有统计学意义(21.76%vs.27.05%,P=0.008;0.00%vs.0.20%,P=0.033),而放线菌门明显高于健康组(13.52%vs.2.88%,P=0.020),差异有统计学意义;患者组拟杆菌属和柔嫩梭菌属占比明显低于健康组(9.15%vs.20.60%,P=0.031;3.29%vs.9.58%,P=0.005),差异有统计学意义,而双歧杆菌属、普雷沃菌属和巨单胞菌属明显高于健康组(10.89%vs.1.78%,P=0.025;10.88%vs.1.98%,P=0.046;10.78%vs.2.69%,P=0.026),差异有统计学意义。结论基于16SrRNA的高通量测序有助于分析精神分裂症患者肠道菌群多样性变化,为研究肠道菌群与精神分裂症的关系提供新的思路和理论依据。

Objective To explore the changes of gut microbiota in patients with schizophrenia.Methods Fresh fecal samples were collected from schizophrenia patients(n=16)and healthy controls(n=18)for DNA extraction,16 SrRNA amplification and Illumina sequencing.Analyses of diversity and species differences between two groups were based on the sequencing data.Results Compared to the healthy controls,the gut microbiota species in schizophrenia patients decreased at the levels of phylum,class,order,family,genus,species and operational taxonomic units(OTUs).The Ace estimator,Chao1 estimator and Shannon index of alpha diversity were significantly lower in schizophrenia patients(226.58±31.67,222.29±34.45,2.66±0.69)compared with the healthy controls(293.63±56.07,302.2±57.99,3.59±0.36,Ps<0.001),while the Simpson index was significantly higher(0.20±0.17 vs 0.07±0.03,P<0.01).Analyses ofβ-diversity was able to differentiate the schizophrenia patients from the healthy controls based on their gut microbiota.The compositions and proportions of gut microbiota in the schizophrenia group were different from those in controls at the levels of phylum and genus.At phylum level,Bacteroidetes and Tenericutes significantly reduced in schizophrenia patients compared to healthy controls(21.76%vs.27.05%,P=0.008;0.00%vs.0.20%,P=0.033),while Actinobacteria increased in schizophrenia patients compared to healthy controls(13.52%vs.2.88%,P=0.020).The genus Bacteroides and genus Faecalibacteriumsignificantly decreased in schizophrenia patients compared with the healthy controls(9.15% vs.20.60%,P=0.031;3.29%vs.9.58%,P=0.005),whereas genus Bifidobacterium,genus Prevotella-9and genus Megamonas significantly increased in schizophrenia patients compared with the healthy controls(10.89% vs.1.78%,P=0.025;10.88% vs.1.98%,P=0.046;10.78% vs.2.69%,P=0.026).Conclusion High-throughput sequencing of 16 SRNA is conducive to analysis of gut microbiota diversity,which can provide new ideas and theoretical foundations for studies on the relationship between gut microbiota and schizophrenia.