| ObjectiveThe changes of intestinal bacteria in patients with first-episode non-medicated depression were preliminarily studied in order to explore the possible role of intestinal bacteria in the pathogenesis of depression by comparing the 16 S rDNA high-throughput sequencing data.Analysis of gene expression profile analysis data of intestinal flora in mice brain tissue transplanted with depressive patients in Gene Expression Omnibus(GEO)database,differential expression genes,biologicalnetworks and biological pathways were finally obtained.Through integrating the analysis results of intestinal bacteria and brain tissue expression data,the influence of intestinal bacteria on the incidence of depression through the brain-gut axis was prelimin-arily explored.Method1.Thirty-five depressive patients(case group)and thirty-five healthy controls(healthy control group)were selected from the outpatient and inpatient department of Tai’an Psychiatric Hospital from November 2014 to November 2016.On the day of admission,all patients were enquired about their of the medical history,examined psychiatrically and physically,collected general clinical data,assessed by Hamilton Depression Scale,measured their height and weight,and calculated their body mass index(BMI).On the second day of hospitalization,blood and stool samples were collected in the morning in accordance with Standard Operating Procedures for Clinical Inspection(4th edition).2.Inflammatory cytokines IL-1β,IL-6 and TNF-α were measured by enzyme-linked immune sorbent assay(ELISA),the serum fasting blood glucose level(FBG)was determined by glucose oxidase assay(GOD),and the serum total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL)and low density lipoprotein(LDL)were measured by enzyme colorimetric assay.3.The V3-V4 region of 16 S rDNA gene of fecal bacteria in depressed patients was comprehensively analyzed by Illumina Mi Seq high-throughput sequencing and statistical methods,and the characteristics of intestinal bacteria in depressed patients were preliminarily studied.4.Genome-wide expression data of brain tissues of mice transplanted with intestinal flora of depressive patients were obtained by GEO.Differentially expressed genes were obtained by R package-deseq2 analysis.Differentially expressed genes were analyzed by STRING network software and DAVID pathway software,and regulatory networks and biological pathways of differentially expressed genes were obtainned.Results1.There was no significant difference in age,sex,smoking history and education level between case group and control group(P﹥0.05).There was no significant difference in BMI,blood glucose,total cholesterol,triglyceride,high density lipoprotein,low density lipoprotein and other metabolic factors(P﹥0.05).Meanwhile,there was no significant difference in serum inflammatory factors such as IL-1β,IL-6,and TNF-α(P﹥0.05).It shows that the case group and the control group have comparability.2.By using Illumina Mi Seq high-throughput sequencing technology,the characteristics of intestinal bacteria structure in patients with depression were analyzed.There were differences in intestinal bacteria structure between patients with depression and healthy people,and the diversity index of intestinal bacteria(Shannon index)in patients with depression increased.At the phylum level,the proportion of Firmicutes bacteria in the intestinal bacteria of depressive patients decreased,while the proportion of Bacteroidetes,Proteobacteria and Actinobacteria increased.At the division level,the proportion of Bcteroidaceae,Prevotellaceae and Ruminococcaceae in the intestinal bacteria of depressive patients decreased,while the proportion of Acidaminococcaceae,Rikenellaceae and Porphyromonadaceae increased.At the genus level,the proportion of Bacteroides,Prevotella and Faecalibacterium in the intestinal bacteria of depressive patients decreased,while the proportion of Alistipes,Phascolarctobacterium and Lachnospiracea incertae sedis increased.3.By analyzing the data of GSE129359,the gene expression profiles were compared between brain tissue of mice transplanted with intestinal flora of depressive patients and the control group,940 differentially expressed genes were obtained,of which 446 were up-regulated genes,494 were down-regulated genes.The first ten up-regulated genes were Ttr,Six3,Lbp,Olfr729,Snai1,Angptl7,Slc2a4,Gpr149,Fam83 d,Gngt2.The first ten down-regulated genes were Gpr151,Gm37181,Gm19719,Gm13749,Mirt1,Gm10814,Gm30382,Gm37608,Erfe,Vmn1r209.4.Using 940 differentially expressed genes as input gene,a protein-protein interaction network was obtained by STRING software.There were 238 proteins in the network and758 interaction pairs were formed.Through DAVID pathway analysis,24 significant pathways were obtained,and neurosynaptic,neuronal development,calcium binding and mitochondrial proton transport related pathways were identified.Conclusion1.Disorder of intestinal bacteria and imbalance of intestinal bacteria in patients with first-episode depression suggest that imbalance of intestinal bacteria may be involved in the pathogenesis of depression.It is related to the decrease of the proportion of Bacteroides,Prevotella and Faecalibacterium,and the increase of the proportion of Alistipes,Phascolarctobacterium and Lachnospiracea incertae sedis.2.Through bioinformatics analysis of genome-wide expression data of intestinal flora of mice transplanted with depressive patients in GEO database,it was found that after transplantation of intestinal flora of depressive patients in mice,there were changes in gene expression of neurosynapses,neuronal development,calcium binding,mitochondrial proton transportrelated pathways and some psychotropic drug targets in the brain.3.Data analysis of intestinal bacteria and brain tissues showed that the disorder of intestinal bacteria may further affect neurotransmitter transport,calcium binding and mitochondrial proton transport in the brain of depressive patients,thus affecting the incidence of depression. |
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