Abstract
Depression is a common and heterogeneous mental disorder. Although several antidepressants are available to treat the patients with depression, the factors which could affect and predict the treatment response remain unclear. Here, we characterize the longitudinal changes of microbial composition and function during escitalopram treatment in chronic unpredictable mild stress (CUMS) mice model of depression based on 16 S rRNA sequencing and metabolomics. Consequently, we found that escitalopram (ESC) administration serves to increase the alpha-diversity of the gut microbiome in ESC treatment group. The microbial signatures between responder (R) and non-responder (NR) groups were significantly different. The R group was mainly characterized by increased relative abundances of genus Prevotellaceae_UCG-003, and depleted families Ruminococcaceae and Lactobacillaceae relative to NR group. Moreover, we identified 15 serum metabolites responsible for discriminating R and NR group. Those differential metabolites were mainly involved in phospholipid metabolism. Significantly, the bacterial OTUs belonging to family Lachnospiraceae, Helicobacteraceae, and Muribaculaceae formed strong co-occurring relationships with serum metabolites, indicating alternations of gut microbiome and metabolites as potential mediators in efficiency of ESC treatment. Together, our study demonstrated that the alterations of microbial compositions and metabolic functions might be relevant to the different response to ESC, which shed new light in uncovering the mechanisms of differences in efficacy of antidepressants.
Highlights
Depression, a debilitating mental disorder[1,2], has detrimental impact on health systems and psychological wellbeing
In present study, we have investigated the dynamic changes of gut microbiota and serum metabolites in chronic unpredictable mild stress (CUMS) mice model of depression treated with ESC based on 16 S rRNA sequencing and metabolomics
We found that the ESC responder and non-responder groups were characterized by differential microbial composition and metabolic pathways
Summary
Depression, a debilitating mental disorder[1,2], has detrimental impact on health systems and psychological wellbeing. It was reported that the disturbances of gut microbial ecosystem were linked with psychological conditions, including bipolar disorder, autism spectrum disorder, schizophrenia, and depression[9,10,11,12,13]. Our previous studies showed that major depressive disorder (MDD) patients were characterized by disturbance of gut microbiome[10,14]. Gut microbiota containing tyrosine decarboxylase (TDC) can convert levodopa to dopamine, affecting the efficacy in the treatment of Parkinson’s disease[21]. Gut microbiome was shown to improve the efficacy of Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) blockers in different cancer patients[22]. Data concerning the impact of the gut microbiome on response to antidepressant in depressive individuals have not been reported. It is interesting to explore how gut microbiome associated with the different antidepressant response
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