Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment

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.

Impact of Inosine on Chronic Unpredictable Mild Stress-Induced Depressive and Anxiety-Like Behaviors With the Alteration of Gut Microbiota

“…Potent anti-inflammatory properties have also been reported in this context ( Baxter et al., 2019 ). Muribaculaceae and associated coproduced short-chain fatty acids have been significantly correlated with depression ( Duan et al., 2021 ), but there is no direct evidence to prove the relevant brain mechanism in MDD. Currently, inosine is commonly used in the treatment of Parkinson’s disease ( Schwarzschild et al., 2014 ) and multiple sclerosis ( Markowitz et al., 2009 ), and it has exhibited direct anti-inflammatory effects on pleural inflammation ( da Rocha Lapa et al., 2012 ).…”

“…Potent anti-inflammatory properties have also been reported in this context (Baxter et al, 2019). Muribaculaceae and associated coproduced short-chain fatty acids have been significantly correlated with depression (Duan et al, 2021), but there is no direct evidence to prove the relevant brain mechanism in MDD. Currently, inosine is commonly used in the treatment of Parkinson's The mutual discriminative KEGG pathways among three groups representing in CUMS+saline and CUMS+inosine groups.…”

The Effects of Stress and Diet on the “Brain–Gut” and “Gut–Brain” Pathways in Animal Models of Stress and Depression

“…In the animal studies of stress and depression covered in this review, most studies reported that stress increased Firmicutes abundance, however Bacteroidetes abundance was more variable (Table 1). Interestingly, Duan et al [104] showed Firmicutes abundance was higher, and Bacteroidetes abundance was lower in mice which did not respond to Escitalopram antidepressant treatment than those that did respond to treatment. Given that the causes of treatment resistance in up to 30% of depressive patients remain elusive, future studies of gut microbiota disturbances in non-responders are warranted [105].…”

“…Actinobacteria and Proteobacteria have been shown to be altered in depressive patients compared to healthy individuals [5,14], however in animal models of stress and depression alterations in these two phyla were inconsistent (Table 1). Increased [34,42,52,54,108] Increased [21,108] Cecum [51,106] Decreased [63,95,104,[107][108][109] Decreased [42,51,52,54,64,68] Decreased [104] Decreased [42] Faecal pellets [21,42,52,54,63,64,68,95,103,104,[107][108][109][110] No change [110] No change [103,106,110] -No change [54] CRS -Increased [69,98,…”

Gut Microbiota-Related Inflammation Factors as a Potential Biomarker for Diagnosing Major Depressive Disorder

“…Accumulating evidence suggests that gut microbiota is involved in the pathogenesis of depression ( Bai et al., 2021a ; Bai et al., 2021b ; Liu L. et al., 2021 ). Animal studies have shown the reproducible and consistent effects of gut microbiota on mouse behavior through inflammation ( Farag et al., 2020 ; Duan et al., 2021 ; Dordević et al., 2021 ; Zhang C. et al., 2021 ). Our group recently observed that CD36 deficiency could affect depressive-like behaviors possibly by modifying gut microbiota compositions in mice ( Bai et al., 2021a ); and gut microbiota-related metabolites held the promise as potential biomarkers for diagnosing depression ( Bai et al., 2021b ).…”