| Background:Most of major depressive disorder was associated with different types of sleep disorder.Few previous studies on sleep disorders were performed.Sleep disorder was related to the severity and prognosis of depressive patients.Sleep disorder was not only of great significance in the diagnosis of depression,but also one of the important indicators to evaluate the therapeutic efficacy of patients with depression.However,the pathogenesis of depression with sleep disorders is not clear,immune inflammation may play a role.Recent studies have shown that the microbiome-gut-brain axis plays an important role in the interaction between depression and sleep disorders.Methods:Based on the recruiting and excluding criteria,78 patients with depressive disorders in the ward of Beijing Huilongguan Hospital and 60 healthy controls were selected from January 2020 to January 2021.Blood and fecal samples were collected.16SrRNA sequencing technique was used to analyze intestinal flora,and Elisa and high performance liquid chromatography-tandem mass spectrometry(HPLC-MS)were used to detect inflammatory factors and canine uric acid metabolism.Sleep quality and daytime function were evaluated with Pittsburgh Sleep quality questionnaire,fatigue severity scale,Epworth sleepiness scale,Insomnia severity scale,Hamilton anxiety scale and Hamilton Depression scale.Study 1:The differences of gut microbiome,immune inflammatory pathway and kynurenine metabolic pathway between patients with depression and healthy subjects were analyzed.Study 2:Based on the characteristics of study 1,we explored the correlation between intestinal microorganisms and clinical phenotypes in patients with depression,especially the correlation between gut microbiome and sleep quality.Study 3:Based on Study 2,patients with depression were divided into two groups with or without sleep disorders,and the intestinal microbiological characteristics of patients with sleep disorders were analyzed to further explore the correlation between intestinal microbiota and immune inflammation in patients with sleep disorders.Results:(1)Compared with the healthy control group,the gut microbiome of major depressive disorder group was abnormal,mainly manifested as low diversity of flora;The pro-inflammatory bacteria(Faecalibacterium,Subdoligranulum,etc.)increased while the anti-inflammatory bacteria(Flavonifractor,Alistipes,etc.)decreased;The results of functional predictive analysis showed the differences between the two groups were mainly reflected in glucose metabolism and amino acid metabolism;Inflammatory factors such as vascular endothelial growth factor,tumor necrosis factor-α,IL-6 and IL-8,Kynurenic acid,quinolinic acid,3-Hydroxy kynurenine and 5-Hydroxytrptamine between the 2 groups showed the differences.(2)In the major depressive disorder group,gut microbiome were correlated with clinical phenotypes.Among them,several genera were associated with sleep quality(Bacteroidetes,Firmicutes,Erysipelotrichaceae,Peptococcaceae,Coprocococcu,Barnesiella,etc.).(3)Gut microbiome(Sutterella,Coprococcus,Dorea,Butyrivibrio etc.),VEGF and TNF-α showed differences in depressive patients with or without sleep disorders.Dorea was positively correlated with serum TNF-α in major depressive disorder patients with sleep disorders.Conclusion:(1)Compared with the healthy control group,the diversity of gut microbiome decreased and the composition changed in patients with major depressive disorder.(2)The relationship between gut microbiome and sleep quality in clinical phenotype was more significant in major depressive disorder patients.(3)Intestinal microbiological imbalance might be one of important biomarkers of major depressive disorder patients with sleep disorder.And the relationship between immune inflammatory factors and intestinal microbiota provides theoretical support for the hypothesis that relationship of intestinal microbiota-immune inflammation-brain played the important roles in the pathogenesis of major depressive disorder patients with sleep disorders. |
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