| Objective: Major Depressive Disorder(MDD)is a type of mood Disorder characterized by significant and persistent depression,mental retardation,cognitive impairment,reduced volitional activity and somatic symptoms.The pathogenesis of major depression is not very clear,generally considered to be the result of interaction of multiple factors,including social,environmental and individual factors.Intestinal microflora is the largest and most direct internal environment in human body.The role of intestinal microflora in the occurrence and development of depression has been paid more and more attention,but the specific mechanism is still unclear.Vortioxetine hydrobromide is a powerful 5-hydroxytryptamine(5-HT)Reuptake inhibitor,is commonly used in the treatment of depression,but the effect of individual differences.The aim of this paper is to clarify the difference of intestinal microflora between MDD patients and healthy people,and the characteristics of intestinal microflora in MDD patients before and after treatment with Vortioxetine hydrobromide,it provides a new way to diagnose or predict the effect of MDD treatment.Methods: In this study,26 MDD patients and 28 healthy subjects,as well as 4-and8-week-old MDD patients treated with Vortioxetine hydrobromide,were divided into groups by using 16 s RNA sequencing technique(group A: MDD patients,group B:patients after 4 weeks of treatment with Vortioxetine hydrobromide,group C: patients after 8 weeks of treatment with Vortioxetine hydrobromide,group D: healthy control group).Stool samples were collected and total DNA was extracted.PCR was used to amplify and purify the extract.Illumina was used for high throughput sequencing and bioinformatics analysis,species information,diversity,abundance and composition of intestinal microflora were obtained from 4 groups of samples.Results: 1.The comparison between MDD patients and healthy people showed that,at the phylum level,compared with the healthy people group,the bacteroidetes(42.1%vs37.4%,P<0.05)and proteobacteria(9.2%vs6.1%,P<0.05)in the MDD patients group were significantly increased.The bacteroidetes(22831.38 ± 7726.53 vs15248.29 ± 8339.37,P=0.0011,P<0.01)and proteobacteria(5001.38 ± 2758.37 vs3670.11 ± 1938.17,P=0.0442,P<0.05)increased.However,the proportion of firmicutes(39.6% vs 0.1%,P<0.05)was significantly reduced,and that of firmicutes(21524.81 ± 7897.09 vs 29789.79 ± 8674.32,P=0.0006,P<0.001)was also reduced.On the level of Genus,compared with the healthy group,the proportion of Bacteroides(25.7% vs 22.1%,P<0.05),Alistipes(2.1%vs1.0%P<0.05),Prevotella＿9(10.3% vs 9.1%,P<0.05)in the MDD group was significantly higher than that in the healthy group.Only the amount of Alistipes(1060.88 ± 857.83 vs 639 ±676.78,P=0.049,P<0.05)increased.Faecalibacterium(4.2%vs6.4%,P<0.05),Roseburia(2.2% vs 4.42%,P<0.05),Bifidobacterium(1.7% vs 1.9%,P<0.05),and the proportion of bacteria genus decreased significantly.Similarly,in Faecalibacterium quantity(2286.5±1706.79vs3826.29±2926.44,P=0.0232,P<0.05),Roseburia(1189±1158.85vs2623.14±2688.5,P=0.0184,P<0.05),,Bifidobacterium(931.12±976.81vs1444±1450.96,P=0.0058,P<0.01)was reduced.2.Comparison of intestinal flora composition of MDD patients after treatment with Vortioxetine hydrobromide showed that the firmicutes(43.8% vs 39.7%,P<0.05)were significantly increased in the MDD patients group at 4 weeks of treatment compared with the group at 4 weeks of treatment,and the firmicutes(25788.19±4621.77 vs 21524.81±7897.09,P=0.0214,P<0.05)were also significantly increased at 4 weeks of treatment.The proportion of bacteroidetes(42.1% vs 44.2%,P<0.05)and proteobacteria(7.3% vs 9.2%,P<0.05)decreased gradually.With the extension of treatment time,the proportion of firmicutes(50.5% vs 43.8%,P<0.05)in the treatment group for 8 weeks increased again,as did the bacterial quantity(29789.79±8674.32 vs 21524.81±7897.09,P =0.013,P<0.05).The proportions of bacteroidetes(37.1% vs 42.1%,P<0.05)and proteobacteria(5.6% vs 7.3%,P<0.05)decreased significantly,as did the bacterial counts(15248.29 ± 8339.37 vs22831.38 ±7726.53,P=0.013,P<0.05)and proteobacteria(3670.11 ±1938.17 vs5001.38±2758.37,P=0.0442,P<0.05).On the level of Genus,the relative abundance of intestinal flora of three groups of samples was compared among the group of MDD patients,the group treated for 4 weeks and the group treated for 8 weeks.Alistipes(2.1% vs 1.6% vs 1.0%,P<0.05),Prevotella＿9(10.3% vs 5.5% vs 3.3%,P<0.05),Bacteroides(25.7% vs s31.3% vs 26.6%,P<0.05),Faecalibacterium(4.2% vs 4.6% vs5.75%,P<0.05),Roseburia(2.1% vs 1.5% vs 2.7%,P<0.05),and Bifidobacterium(1.7%vs 1.9% vs 2.6%,P<0.05).The proportion of these bacteria will gradually increase with the remission of symptoms.After 4 weeks of treatment,Bacteroides(18427.62±5487.57 vs 13944.31 ± 7707.01,P =0.0276,P<0.05)increased.After 8 weeks of treatment,Alistipes(639±676.78vs1060.88±857.83,P=0.013,P<0.05),Prevotella＿9(1902±5616.57vs5607.96±3505.13,P=0.0066,P<0.01)decreased.Faecalibacterium(3235.92±2505.7 vs 2286.5±1706.79,P=0.013,P<0.05),Bifidobacterium(1452.5±795.38vs931.12±976.81,P=0.0398,P<0.05) increased.Conclusion: The ratio of bacteroidetes and proteobacteria in intestinal tract of patients with MDD was higher than that of healthy control group,and the ratio of pachymycetes was lower than that of healthy control group.There was significant difference between the two groups.The proportion of pachyderm in the gut of MDD patients gradually increased,while the proportion of bacteroidetes and proteobacteria gradually decreased with the treatment time prolonged.Therefore,we conclude that Vortioxetine hydrobromide treatment may reduce the severity of depression in patients with major depression by improving the regulation of Intestinal Flora. |
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