Association Analysis Of Gut Microbiota And Efficacy Of SSRIs Antidepressants In Patients With Major Depressive Disorder

Objective:Major depressive disorder(MDD),as a common mental disorder with high disability rate and high suicide rate has become a worldwide problem and serotonin reuptake inhibitors(SSRIs)drugs First-line clinical medication is not effective for some patients with depression.but it takes at least 6-8 weeks to evaluate the efficacy of anti-SSRIs antidepressants,which not only generates additional economic and time costs during this period,but also increases the difficulty of treatment.It is therefore necessary to better understand the pathways that may mediate the antidepressant effects of SSRIs.Relevant studies have shown that compared with the healthy control group,there are significant differences in the diversity and abundance of gut microbiome in MDD patients,and some studies have found that the gut microbiome has an impact on the efficacy of drugs,which suggests that the composition of the gut microbiome between individuals Differences may affect the efficacy of SSRIs antidepressant treatment,thus the potential of gut microbiota as a biomarker to predict the efficacy of SSRIs antidepressants.The purpose of this study was to investigate the relationship between the gut microbiota and the efficacy of SSRIs antidepressants in patients with MDD.Methods:Subjects diagnosed with MDD who did not receive antidepressant treatment were recruited in the outpatient and inpatient departments of the First Hospital of Shanxi Medical University.After signing the informed consent form,the general demographic data of the subjects were collected,and a follow-up period of 8W was conducted.During the period,SSRIs antidepressants were given,and HAMD was re-evaluated after 8W,and the efficacy was evaluated according to the HAMD total score at baseline and at the end of 8W.The reduction rate of the HAMD total score at the end of 8W was used as the efficacy evaluation index:compared with the baseline,if the reduction rate of the HAMD total score at the end of 8 weeks was≥50%,the treatment was evaluated as effective,and it was classified into the treatment effective group(T).On the contrary,it was assessed as treatment ineffective and classified into the treatment ineffective group(TR).Reduction rate=(baseline HAMD total score-8W end HAMD total score)/baseline HAMD total score.Recruit healthy subjects.The fresh feces of the subjects were collected at the time of enrollment,stored in a sterile container,and quickly stored in a-80℃ refrigerator within 2 hours,and repeated freezing and thawing were avoided as much as possible until DNA was extracted.16SrRNA gene sequencing was used to detect the gut microbiome,and the diversity and abundance of the gut microbiome in the three groups were compared,and the differential flora among the three groups was searched for correlation analysis.Finally,we included gender and years of education as covariates into the statistical model,and used a binary logistic regression model and receiver operating characteristic curve(ROC)to conduct a multi-indicator joint analysis with differential flora to analyze the effect of differential gut flora on SSRIs.Predictive power of antidepressant drug efficacy.Results:1.1.There was no significant difference in BMI among the three groups,but there were significant differences in gender,age,and years of education2.There were significant differences in Goods coverage index,Shannon index,Simpson index and Pielou-e index in the a diversity analysis among the three groups of subjects;in terms of β diversity,the three-dimensional graph of Jaccard analysis based on principal coordinate analysis(PCoA)was shown in There were significant differences in gut microbial communities between MDD patients in the treatment-effective group and healthy controls,but no significant differences in gut microbial communities between the treatment-ineffective and healthy controls.Using PERMANOVA analysis and Anosim analysis,it was found that the difference between the three groups was significantly greater than the difference within the group.3.LDA find that there were 50 different bacterial groups among the three groups,of which 19 genera were mainly attributable to the genus level.The relative abundance of 12 genera increased in the HC group,5 genera in the treatment effective group increased in relative abundance,and 2 genera in the treatment ineffective group increased in relative abundance.The correlation analysis of 19 bacterial genera and the score reduction rate showed that Blautia,Bifidobacterium and Coprococcus with higher relative abundance in the treatment effective group were related to the efficacy of SSRIs antidepressants.At the same time,we included covariates including gender,age,and years of education into the statistical model,used binary logistic regression model and ROC to analyze the association prediction between the efficacy of SSRIs antidepressants and related flora,and calculated the area under the ROC curve(AUC)value 0.931,sensitivity 0.879,specificity 0.920.Conclusion:This study found that the diversity and relative abundance of the gut microbiome may be effective biomarkers for predicting the antidepressant efficacy of SSRIs in MDD patients.Among them,Blautia,Bifidobacterium and Coprococcus can predict the efficacy of SSRIs antidepressants.Combined with multi-index analysis The RUC was 0.931,the sensitivity was 0.879,and the specificity was 0.920.