Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder

Abstract

Objective: Increasing evidence shows a close relationship between gut microbiota and major depressive disorder (MDD), but the specific mechanisms remain unknown. This study was conducted to explore differential gut microbiota compositions related to the severity of MDD.

Methods: Healthy controls (HC) (n = 131) and MDD patients (n = 130) were included. MDD patients with Hamilton Depression Rating Scale (HDRS) score <25 and ≥25 were assigned into moderate (n = 72) and severe (n = 58) MDD groups, respectively. Univariate and multivariate analyses were used to analyze the gut microbiota compositions at the genus level.

Results: Thirty-six and 27 differential genera were identified in moderate and severe MDD patients, respectively. The differential genera in moderate and severe MDD patients mainly belonged to three (Firmicutes, Actinobacteriota, and Bacteroidota) and two phyla (Firmicutes and Bacteroidota), respectively. One specific covarying network from phylum Actinobacteriota was identified in moderate MDD patients. In addition, five genera (Collinsella, Eggerthella, Alistipes, Faecalibacterium, and Flavonifractor) from the shared differential genera by two MDD groups had a fair efficacy in diagnosing MDD from HC (AUC = 0.786).

Conclusions: Our results were helpful for further exploring the role of gut microbiota in the pathogenesis of depression and developing objective diagnostic methods for MDD.

Keywords: Actinobacteriota; Bacteroidota; Firmicutes; gut microbiota; major depressive disorder.

Figure 1

Changes of gut microbiota compositions in HC and moderate and severe MDD patients. (A) Relative abundances of gut microbiota at the genus level in MDD patients and HC. (B) OPLS-DA model showed that there was only a small overlap between HC and moderate MDD patients, suggesting the divergent microbial changes between the two groups; (C) differential genera responsible for discriminating moderate MDD patients from HC; (D) OPLS-DA model showed that there was only a small overlap between HC and severe MDD patients, suggesting the divergent microbial changes between the two groups; (E) differential genera responsible for discriminating severe MDD patients from HC. HC, healthy controls; MDD, major depressive disorder; Fae, Faecalibacterium; Vic, Victivallis; Meg1, Megamonas; Pyr, Pyramidobacter; Hyd, Hydrogenoanaerobacterium; Pre, Prevotella; Kle, Klebsiella; Ace, Acetanaerobacterium; But, Butyricimonas; Ali, Alistipes; Cop, Coprobacillus; Ana1, Anaerococcus; Act, Actinomyces; Eub, Eubacterium; Par1, Parabacteroides; Psy, Psychrobacter; Odo, Odoribacter; Ent1, Enterococcus; Ent2, Enterorhabdus; Cor, Corynebacterium; Ana2, Anaerofustis; All, Allisonella; Por, Porphyromonas; Bar, Barnesiella; Ols, Olsenella; Dor, Dorea; Oxa, Oxalobacter; Egg, Eggerthella; Sla, Slackia; Fla, Flavonifractor; Pep, Peptoniphilus; Bla, Blautia; Ana3, Anaerotruncus; Par2, Parvimonas; Gor, Gordonibacter; Col, Collinsella; Lac1, Lactococcus; Sut, Sutterella; Tur, Turicibacter; Meg2, Megasphaera; Bil, Bilophila; Lac2, Lactobacillus; Bac, Bacteroides; Ana, Anaeroglobus.

Figure 2

Co-occurrence network showing microbial changes in moderate and severe MDD patients. The microbial genera changed in moderate or severe MDD were identified by OPLS-DA. In total, 63 differential genera were identified in the two groups. Nineteen of 63 genera were consistently altered in both moderate and severe MDD patients relative to HC, and 17 and 8 genera were specific to moderate MDD alone and severe MDD alone, respectively. Compared to HC, moderate MDD was mainly characterized by altered covarying genera assigned to phylum Firmicutes, Actinobacteriota, and Bacteroidota, while severe MDD was mainly characterized by altered covarying genera assigned to phyla Firmicutes and Bacteroidota. Lines between nodes indicate Spearman’s correlation > +0.30 (light red) or < −0.30 (light blue)); line thickness indicates p value (p < 0.05).

Figure 3

Five differential genera as potential biomarkers for diagnosing MDD. The model consisting of these five genera had the minimum AIC value; thus, they were viewed as the potential biomarkers. The panel consisting of these five genera could yield an AUC of 0.786 for classifying MDD patients from HC, suggesting fair diagnostic performance in diagnosing MDD. HC, healthy controls; MDD, major depressive disorder; AUC, area under the curve.

Figure 4

Differential genera in moderate and severe MDD patients significantly correlated with HDRS. Six genera (four of them belonged to phylum Firmicutes) in moderate MDD patients were significantly positively or negatively correlated with HDRS. Four genera in severe MDD patients were significantly positively correlated with HDRS. MDD, major depressive disorder; HDRS, Hamilton Depression Rating Scale.

Figure 5

Genus-level analysis of gut microbiota between moderate and severe MDD patients. (A) OPLS-DA model showed that the moderate and severe MDD patients could not be significantly separated; (B) there were four differential genera between the two groups.