Gut Microbiota Changes in Patients With Major Depressive Disorder Treated With Vortioxetine

Abstract

Vortioxetine hydrobromide is a common clinical medication for major depressive disorder (MDD). However, it remains unclear whether vortioxetine hydrobromide acts by affecting the structure and composition of gut microbiota. Here, we analyzed fecal samples from 28 healthy controls (HCs) and 26 patients with MDD before treatment with vortioxetine hydrobromide, at 4 weeks after treatment, and at 8 weeks after treatment. High-throughput pyrosequencing showed that, according to the Chao1 and Shannon indices, fecal bacterial α-diversity was higher in the patients with MDD than in the HCs (p < 0.05), but no significant differences were observed after vortioxetine hydrobromide treatment (p > 0.05). PCoA results revealed that the gut microbiota composition was significantly different between the MDD groups and HCs. Proteobacteria and Actinobacteria were strongly increased, whereas Firmicutes were significantly reduced in the MDD group compared with the HCs. After treatment with vortioxetine hydrobromide, Firmicutes were significantly increased, and the proportion of Bacteroidetes decreased. Most notably, Lachnospira, Roseburia, and Faecalibacterium were negatively correlated with the severity of depressive symptoms. Taken together, our data indicate changes in the fecal microbiota composition in MDD patients compared with HCs, and vortioxetine hydrobromide may treat MDD through regulation of the gut microflora.

Keywords: gut microbiota; gut-brain axis; major depression disorder; treatment; vortioxetine hydrobromide.

Figure 1

Flowchart for participant recruitment and sample collection process.

Figure 2

MDD leads to significant structural and functional changes in the gut microbiota. (A) Rarefaction curve from MDD and HCs. (B) α-Diversity on the Chao index between groups. (C) α-Diversity on the Shannon index between groups. (D) β-Diversity on unweighted UniFrac between groups. (E) PCoA of the gut microbiota metagenomes between groups. *p < 0.05, **p < 0.01.

Figure 3

Taxonomic differences in fecal microbiota between HCs and MDD patients. Comparison of relative abundance at the bacterial phylum (A), family (B) and genus (C) levels between HCs and MDD patients. LEfSe identified the most differentially abundant taxa between HCs and MDD patients. The brightness of each dot is proportional to its effect size (D). Taxa enriched in HCs are indicated with a negative logarithmic discriminant analysis (LDA) score (red), and taxa enriched in MDD patients have a positive score (green). Only taxa meeting an LDA significance threshold > 3.5 are shown (E).

Figure 4

Alpha and beta diversity measures in MDD patients before and after vortioxetine hydrobromide treatment. (A) Rarefaction curve between groups. (B) α-Diversity on the Chao index between groups. (C) α-Diversity on the Shannon index between groups. (D) PCoA of the gut microbiota metagenomes between groups. (E) β-Diversity on unweighted UniFrac between groups. #p < 0.05.

Figure 5

Taxonomic differences in the fecal microbiota between MDD patients before and after treatment. Comparison of relative abundance at the bacterial phylum (A), family (B) and genus (C) levels before MDD treatment, MDD + VOR for 4 weeks, MDD + VOR for 8 weeks. LEfSe identified the most differentially abundant taxa between MDD + VOR after 8 weeks and before MDD treatment. The brightness of each dot is proportional to its effect size (D). Taxa enriched before MDD treatment are indicated with a negative logarithmic discriminant analysis (LDA) score (red), and taxa enriched after 8 weeks of treatment (MDD + VOR for 8 weeks) have a positive score (green). Only taxa meeting an LDA significance threshold > 3.5 are shown (E).

Figure 6

Correlations between fecal microbiota and HAMD score.