Characterization of Gut Microbiome Composition in Depression and Completed Suicide

Abstract

Growing evidence supports a bidirectional relationship between the gut microbiome and mental health. This study investigated the association between gut microbiota, depression, and suicidal behavior by analyzing fecal samples from 35 individuals with varying depression levels and 36 completed suicide cases. Standardized psychometric assessments were used for depression evaluation. Analysis revealed significant taxonomic differences between groups, with increased abundance of Firmicutes, Clostridia, Lachnospiraceae, Blautia, and Dorea in suicide cases, which also positively correlated with depression severity. Metabolic pathway analysis demonstrated a notable dichotomy: suicide cases showed elevated pathways related to infection processes, inflammation, and antibiotic resistance, while the control group exhibited higher energy metabolism and vitamin synthesis pathways. The findings establish specific microbiome profiles associated with both depression symptoms and suicidal behavior, suggesting that gut dysbiosis may influence mental health through altered energy metabolism and inflammatory processes, potentially offering new perspectives for diagnostic and therapeutic approaches.

Keywords: Firmicutes; Lachnospiraceae; depression; energy metabolism; gut microbiome; gut–brain axis; inflammation; mental health; metabolic pathways; suicide.

Figure 1

Alpha and beta diversity analysis of gut microbiome in suicide cases versus living controls. (A) shows alpha diversity metrics between groups, with boxplots representing Faith’s Phylogenetic Diversity (Faith’s PD) and Shannon diversity index. No significant (p > 0.05) differences were observed in alpha diversity metrics between the deceased case group and alive control group. (B) illustrates beta diversity analysis through Principal Coordinate Analysis (PCoA) based on Bray–Curtis distances, reflecting quantitative differences in community structure. The circles in the graph (B) represent individual samples: blue ones are from the control group of living participants, red ones are suicide cases. The dotted line shows the Bray-Curtis distance clustering boundary, visualizing differences in microbiome community structure between groups. Statistical significance was determined using PERMANOVA with 999 permutations, adjusting for age, sex, and time between death and sample collection.

Figure 2

Associations between gut microbiome bacteria at different taxonomic levels and indicators of depression/suicidal intentions. (A) Associations between phylum-level bacterial taxa and depression assessment scales. The stacked barplot displays significant correlations (p ≤ 0.05) with absolute coefficient values above 0.3 for major bacterial phyla. (B) Associations between species-level bacterial taxa and depression metrics. Each colored bar represents a different depression and anxiety assessment scale, with the horizontal axis showing the strength and direction of relationships.

Figure 3

Intersection between taxonomic markers of depression and suicide. The diagrams show significant increases in specific taxa in suicide cases, including representatives of the Firmicutes phylum, Clostridia class, Lachnospiraceae family, and the genera Blautia and Dorea. These same taxa demonstrate positive correlations with depression indicators in the control group.

Figure 4

Principal Component Analysis (PCA) decomposition of psychometric scales demonstrates a high degree of concordance. The plot shows the first two principal components, accounting for 57.3% and 12.3% of variance, respectively. Points are colored according to Hospital Anxiety and Depression Scale Depression subscale (HADSD) scores, with darker red indicating higher depression severity. Depression assessment scores (HADSD, BDI, HDRS, YMSUM-inv) cluster together and positively correlate with bacterial taxa, particularly Dorea formicigenerans and phylum Firmicutes, while negatively associating with energy metabolism and metabolism of cofactors and vitamin pathways. This visualization demonstrates the inverse association between depression severity and energy-related metabolic pathways, while highlighting positive associations with specific bacterial taxa.

Figure 5

Analysis of predicted metabolic pathways comparing control subjects and completed suicide cases. (A) Intersection between metabolic markers of depression and suicide. (B) The diagrams show differences in the functional potential of the gut microbiome between groups. Red color indicates metabolic pathways significantly elevated in the suicide group, while teal blue color indicates pathways predominant in the control group.

Figure 6

Correlation heatmap between marker bacterial taxa significantly associated with suicide/depression and their predicted metabolic pathways. Teal/blue colors indicate negative correlations, while red colors represent positive correlations, with color intensity corresponding to correlation strength. Statistical significance levels are denoted by asterisks: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.