# Integrated Microbiome and Metabolomic Profiling to Identify Potential Biomarkers of Major Depressive Disorder

**Authors:** Hyunjung Lee, Mee-Hyun Lee, Seung-Ho Seo, Juhan Pak, Soobin Bae, Gayoun Lee, Hyun Sik Kim, Kyeongok Kim, Jae-Hong Kim, Hong-Seok Son

PMC · DOI: 10.4014/jmb.2512.12014 · Journal of Microbiology and Biotechnology · 2026-01-22

## TL;DR

This study combines gut microbiome and metabolomic data to identify potential blood-based biomarkers for major depressive disorder.

## Contribution

The study introduces a novel integrated multi-omics approach to uncover a functional gut-lipid axis in MDD.

## Key findings

- Eubacterium eligens group and Veillonella are enriched in MDD patients.
- Gut taxa correlate with acylcarnitine and fatty acid metabolism changes.
- Plasma metabolome outperforms gut microbiome in MDD diagnosis (AUC = 0.862).

## Abstract

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.

## Linked entities

- **Diseases:** major depressive disorder (MONDO:0002009)

## Full-text entities

- **Genes:** VIP (vasoactive intestinal peptide) [NCBI Gene 7432] {aka PHM27}
- **Diseases:** inflammatory bowel disease (MESH:D015212), MDD (MESH:D003865), substance abuse (MESH:D019966), carnitine deficiency (MESH:C536778), HAM (MESH:D015493), Mental Disorders (MESH:D001523), neuroinflammation (MESH:D000090862), inflammatory drugs (MESH:D000081015), DSM-5 (MESH:D008232), inflammation (MESH:D007249), HC (MESH:D000067329), SCID (MESH:D020914), neurotransmitter dysregulation (MESH:D021081), gut dysbiosis (MESH:D064806), anhedonia (MESH:D059445), Depression (MESH:D003866)
- **Chemicals:** pyridine (MESH:C023666), short-chain fatty acids (MESH:D005232), lactate (MESH:D019344), glycolic acid (MESH:C031149), urate (MESH:D014527), galactose (MESH:D005690), purine (MESH:C030985), tyramine (MESH:D014439), carnitines (MESH:D002331), MSTFA (MESH:C086665), Lyso PC (MESH:C006065), Taxa (-), methionine (MESH:D008715), glutamine (MESH:D005973), creatinine (MESH:D003404), acetonitrile (MESH:C032159), glucose (MESH:D005947), methanol (MESH:D000432), tryptophan (MESH:D014364), formic acid (MESH:C030544), PC (MESH:C053518), propionate (MESH:D011422), betaine (MESH:D001622), amino acid (MESH:D000596), TCA (MESH:D014238), lipid (MESH:D008055), glutamate (MESH:D018698), fatty acid (MESH:D005227), amino sugar (MESH:D000606), nitrogen (MESH:D009584), inositol (MESH:D007294), propionylcarnitine (MESH:C003223), phenylalanine (MESH:D010649), H (MESH:D006859), alanine (MESH:D000409), water (MESH:D014867), serotonin (MESH:D012701), glycerophospholipid (MESH:D020404), ribitol (MESH:D012255), 3,5-dihydroxydecanoic acid (MESH:C436564), glycerol (MESH:D005990), cystine (MESH:D003553), carbohydrate (MESH:D002241), Lysine (MESH:D008239), sucrose (MESH:D013395), starch (MESH:D013213), simple sugars (MESH:D009005), Helium (MESH:D006371), acylcarnitine (MESH:C116917), aspartate (MESH:D001224), docosahexaenoic acid (MESH:D004281), tartaric acid (MESH:C029768), inosine (MESH:D007288), carbon (MESH:D002244), EDTA (MESH:D004492), pentose phosphate (MESH:D010428)
- **Species:** Faecalibacterium (genus) [taxon 216851], Veillonella (genus) [taxon 29465], Lachnospira eligens (species) [taxon 39485], Lachnospira (genus) [taxon 28050], gut metagenome (species) [taxon 749906], Bacteroides (genus) [taxon 816], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12868950/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12868950/full.md

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Source: https://tomesphere.com/paper/PMC12868950