Characterization and correlation of gut microbiota in major depressive disorder patients with suicidal ideation.

Abstract

Background: This study aimed to analyze the gut microbiota composition in major depressive disorder (MDD) patients with suicidal ideation and explore its correlations with suicidal ideation and plasma levels of C-reactive protein (CRP) and short-chain fatty acids (SCFAs).

Methods: 57 MDD patients and 57 healthy controls (HC) were enrolled. The Hamilton Depression Scale-24 (HAMD-24) and Beck Scale for Suicide Ideation-Chinese Version (BSI-CV) assessed the depressive symptoms and suicidal ideation intensity, respectively. According to BSI-CV, MDD patients were divided into those without suicidal ideation (SC0 group) and those with suicidal ideation (SC1 group). All participants provided fecal and blood samples. Gut microbiota composition was analyzed by 16 S ribosomal RNA (16 S rRNA) sequencing. The plasma CRP levels were measured by enzyme-linked immunosorbent assay (ELISA), and SCFAs by targeted gas chromatography-mass spectrometry (GC-MS). Spearman's correlation analysis was used to evaluate the correlation among gut microbiota, HAMD scores, BSI scores, and plasma levels of CRP and SCFAs. Mediation analysis was performed using Model 4 of the PROCESS (version 3.5). All post-hoc pairwise comparisons in this analysis were adjusted for false discovery rate (FDR), with a FDR-corrected p < 0.05 set as the significance threshold.

Results: 1. MDD patients had significantly lower levels of acetic, propionic, and butyric acids than HC (p<0.01), while their CRP levels were significantly higher (p<0.001). 2. The alpha diversity analysis showed the HC group had significantly higher Good's coverage than SC0 (FDR-corrected p<0.05), higher Pielou's evenness (FDR-corrected p <0.05) and Simpson indices than SC1 (FDR-corrected p<0.01), while SC0 also had a higher Simpson index than SC1 (FDR-corrected p<0.05). The beta diversity analysis showed differences in the gut microbiota composition among the three groups (pseudo-F = 2.29, FDR-corrected p <0.01). 3. Linear discriminant analysis effect size (LEfSe) identified 24 differentially abundant bacterial taxa across classification levels. 4. The correlation analysis showed that Blautia was positively correlated with BSI scores, HAMD scores, and CRP levels. Bacteroides, Roseburia, and Sutterella were negatively correlated with BSI and HAMD scores. 5. The mediation analysis suggested that CRP might partially mediate the relationship between Blautia and suicidal ideation intensity, but this mediating effect was confounded by depression severity.

Conclusions: This study exploratorily found that MDD patients with suicidal ideation showed preliminary characteristics in gut microbiota diversity, composition, and plasma levels of CRP and SCFAs, and that CRP may play a partial mediating role in the relationship between Blautia and suicidal ideation. These findings were confounded by depression severity, and the underlying mechanisms require further investigation.

Clinical trial number: Not applicable.