The pathophysiology of major depressive disorder (MDD) remains incompletely understood, hindering the development of objective diagnostic markers. While the microbiota-gut-brain axis is implicated in MDD, the functional link between gut dysbiosis and systemic metabolism remains largely obscure. To address this, we employed an integrated multi-omics approach combining 16S rRNA gene sequencing, GC-MS analysis of urine and plasma, complemented by UPLC-QTOF-MS profiling of plasma, in a Korean cohort (n = 69). We identified distinct taxonomic shifts, specifically the enrichment of the Eubacterium eligens group and Veillonella in MDD patients. Integrated correlation analysis revealed a functional "gut-lipid axis", where these taxa were strongly associated with alterations in host acylcarnitine and fatty acid metabolism. Notably, diagnostic evaluation demonstrated that the plasma metabolic profile yielded superior predictive accuracy (AUC = 0.862) compared to the gut microbiota (AUC = 0.654). Our findings suggest that while the gut microbiome provides mechanistic insights into lipid dysregulation, the circulating metabolome serves as a more robust, proximal diagnostic readout for MDD.
Jo et al. (2026) studied this question.