基于高通量测序研究大学生抑郁人群肠道菌群的多样性

Gut microbial profile analysis of depression in college students based on high-throughput sequencing technique

[目的]探讨在校大学生抑郁人群肠道菌群的多样性特点。[方法]发放调查问卷并收集抑郁人群和健康对照粪便样本,以提取的肠道菌群DNA为模板扩增16S rRNA片段,运用Illumina HiSeq平台建立文库并进行高通量测序,信息学手段分析菌群的多样性和丰度差异。[结果]Alpha多样性分析的Chao1(P=0.0099)和Ace指数(P=0.0011)指数均显示抑郁症患者物种丰度随着抑郁程度加重有降低后升高的趋势,且轻度和中度抑郁相比有极显著性差异;物种组成分析抑郁人群和健康对照在门属水平上有显著差异,其中放线菌门(AC:P=0.0042;BC:P=0.031)、纤维杆菌属(AC:P=0.0000017;BC:P=0.000024)、双歧杆菌属(AC:P=0.0035;BC:P=0.0056)、肠杆菌属(AC:P=0.011;BC:P=0.0006)、乳酸菌属(AC:P=0.00072;BC:P=0.0048)与抑郁程度负相关;组间样品LEfSe分析,巨球型菌属、疣微菌门、阿克曼氏菌属等8种菌可能是抑郁症的疾病标志菌。[结论]样本分析显示,轻中度患者菌群丰度有显著性差异,一些潜在有益细菌属如双歧杆菌属、魏斯氏菌属、乳酸菌属等丰度与抑郁程度成反比。

[Objective]To study the diversity and structure of intestinal microbial profile analysis with depression among college students.[Method]After the questionnaire is distributed,fresh fecal samples were collected from moderate depression student,mild depressionand healthy controls for DNA extraction.The library was established on Illumina Hiseq platform and 16S rRNA high-throughput sequencing technique was used to analyze the diversity and difference of intestinal microbial.[Result]Chao1(P=0.0099)and Ace index(P=0.0011)of alpha diversity were significantly between mild and moderate depression(P0.01).The gut microbiotic compositions of depression patients were significantly different with healthy controls characterized by significant changes in the relative abundance of Actinobacteria(AC:P=0.0042;BC:P=0.031),Bifidobacterium(AC:P=0.0035;BC:P=0.0056),enterobacter(AC:P=0.011;BC:P=0.0006),Lactobacillus(AC:P=0.00072;BC:P=0.0048)and fibrobacter(AC:P=0.0000017;BC:P=0.000024).Besides,we identified 16 markers with LDA score4 by the analysis of LEfse,among which megasphacra,uncultured-megasphacra,Verrucomicrobia,Akkermansia,Akkermansiaceae,Verrucomicrobiae,uncultured-Akkermansia,Verrucomicrobiales were the dominant groups of moderate depression.[Conclusion]These findings show either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera.Further studies are warranted to evaluate the suitability of the microbiome as a biomarker which can provide new ideas for study on the relation between gut microbiota and depression.The severity of depression is inversely proportional to the abundance of the Bifidobacterium,Weissella and Lactobacillus.