The potential microbiota biomarker and functional characteristics between patients with major depressive disorder, bipolar disorder, and healthy controls

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are characterized by severe mood disturbances and have collectively caused a significant burden of diseases. However, diagnosing and distinguishing between the two disorders can be challenging due to the variability of symptoms. Growing evidence in the gut-brain axis has shed light on the connection between gut microbiota, their functions, and the central nervous system, especially for mood disorders. The present study aimed to identify specific microbiota markers associated with MDD and BD in a sample of Han Chinese individuals. We recruited 479 subjects (197 MDD, 158 BD, and 124 healthy controls) and obtained their basic demographic characteristics, dietary factors, and symptom severity data through questionnaires. We performed 16S rRNA sequencing to obtain their microbiota profiles. We compared the microbial diversity between groups by alpha and beta diversity indices. We used multivariate regression analysis to identify differential taxa that could serve as potential biomarkers after adjusting for batch effect, age, BMI, and sex. The correlation between the selected taxa within each group was visualized using a direct force graph, and the correlation between taxa and other variables was assessed through heatmaps. Functional analysis was also performed to explore differences between groups. Furthermore, a co-occurrence network analysis was conducted to investigate the connections between the selected taxa and the functional pathways. Patients with MDD or BD exhibited lower alpha diversity and significant beta diversity (p < 0.01) compared to healthy controls across all diversity indices. The abundance of Bacteroidota and Desulfobacterota was reduced in the patients, while Firmicutes were more abundant. At the genus level, we found six taxa, including Bilophila, that were reported in both MDD and BD groups, eight taxa, including Bacteroides, that were specific to MDD patients, and three taxa, including Coprococcus, that were specific to BD patients. Among all groups, Bacteroides had the strongest associations within the correlation network. The two most significant pathways were both related to energy production. Additionally, we found that two important depression-related ways, purine biosynthesis and pyrimidine biosynthesis, were reduced in MDD patients. Bacteroides were associated with energy production pathways and gluconeogenesis in MDD patients, while Coprococcus showed the most associations with identified pathways in BD patients. Patients with mood disorders showed reduced microbial diversity and distinct microbial composition compared to healthy individuals, supporting previous findings suggesting gut dysbiosis in mood disorder patients. The identified microbiota taxa align with previous studies and could potentially serve as discriminative biomarkers for patients with mood disorders. These specific taxa may also participate in mood disorder-related functional pathways, such as purine and pyrimidine biosynthesis.