Taxonomic and Metabolic Signatures of Gut Microbiota for Assessing the Severity of Depression and Anxiety in Major Depressive Disorder Patients

Major depressive disorder (MDD) is a heterogeneous mental disorder for which the precise assessment of symptom severity remains challenging. Studies have consistently found that the microbiota-gut-brain (MGB) axis is profoundly altered in MDD, but whether MGB-relevant clinical parameters are applicable to depression subphenotyping remains largely unexplored. In this prospective study, we assessed the taxonomic and metabolic signatures of fecal microbiota from 45 unmedicated MDD patients and explored their associations with the severity of depression and anxiety symptoms as measured by Hamilton depression scale-17 (HAMD-17) and Hamilton anxiety scale-14 (HAMA-14), respectively. The global microbial compositions of MDD patients with mild, moderate and severe symptoms were largely similar. Nevertheless, multiple discriminative bacterial taxa could be identified among the subgroups across the genus to species level. The abundance of fecal Streptococcus was highly correlated with both HAMD and HAMA scores. Patients with severe depression symptoms showed significantly higher abundance of Phascolarctobacterium and Akkermansia, while enrichment of Akkermansia, Coprococcus and Streptococcus were observed with severe anxiety symptoms. In addition, fecal microbial metabolite indole-3-carboxyaldehyde proved useful to discriminate the severity of depression or anxiety symptoms. Together, our results support the utility of microbial taxa and metabolites as potential MGB-based biomarker panel for stratifying the symptom severity of MDD patients.