Major depressive disorder (MDD) is a psychiatric condition characterized by persistent depressed mood, anhedonia, and cognitive/somatic symptoms. In the WikiBiome framework, MDD is a paradigm case for the gut brain axis: gut dysbiosis drives systemic inflammation and neuroinflammation through endotoxemia, tryptophan-kynurenine shunting, and loss of neuroactive microbial metabolites (serotonin, gaba).
Microbiome Signature
- Depleted: dialister, faecalibacterium prausnitzii, coprococcus, roseburia — SCFA and neuroactive metabolite producers capuco 2020 gut microbiome dysbiosis depression review eskandar 2025 gut brain axis depression anxiety schizophrenia scoping review.
- Enriched: Enterobacteriaceae, Eggerthella — LPS-producing pro-inflammatory taxa.
- Metal connection: Shotgun metagenomics in MDD reveals nickel-metal toxicity signatures (NiMeTox) maes 2026 shotgun metagenomics mdd nimetox.
- Mediterranean diet: Associated with reduced MDD risk via microbiome modulation latorre perez 2021 spanish gut microbiome mediterranean diet.
Mechanistic Pathways
- Tryptophan shunting: Inflammation-driven IDO activation diverts tryptophan from serotonin synthesis to the neurotoxic kynurenine pathway → quinolinic acid → excitotoxicity.
- SCFA depletion: Lost butyrate → impaired BBB integrity → neuroinflammation.
- Endotoxemia → neuroinflammation: LPS → TLR4 → IL-6/TNF-alpha → microglia activation.
- Vagal signaling: Depleted Lactobacillus/Bifidobacterium → reduced vagal tone → HPA axis dysregulation.
Cross-References
- depression — related entity page
- gut brain axis — primary mechanistic framework
- serotonin — depleted via tryptophan shunting
- gaba — depleted via commensal loss
- dialister — strongest protective association in depression
- interleukin 6 — key inflammatory mediator
- endotoxemia — LPS-driven neuroinflammation
- anxiety — frequently comorbid