Gut microbiota dysbiosis and depression: Bidirectional interactions, mediating pathways, and microecological therapeutics

Mar 20, 2026Current research in food science

Gut bacteria imbalance and depression: Two-way links, how they interact, and bacteria-based treatments

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Abstract

The microbiota-gut-brain axis may influence major depressive disorder (MDD) through mechanisms such as neuroinflammation and neurotransmitter metabolism.

Gut microbiota dysbiosis is associated with major depressive disorder.
Stress-related intestinal permeability may initiate gut dysbiosis, leading to impaired barrier function and neuroinflammation.
Disrupted neurotransmitter synthesis and overactivation of the HPA axis could exacerbate depressive symptoms.
Interventions targeting gut microbiota may reshape microbial communities and increase levels of beneficial compounds like short-chain fatty acids.
Microbiome-targeted interventions may offer non-pharmacological strategies for alleviating MDD.

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The microbiota-gut-brain axis (MGBA) is increasingly recognized as a key target for ameliorating major depressive disorder (MDD). This review systematically synthesizes evidence on the bidirectional relationship between gut microbiota dysbiosis and MDD, and delineates the core mechanisms-such as neuroinflammation, neurotransmitter metabolism, and hypothalamic-pituitary-adrenal (HPA) axis dysregulation-through which this axis influences depressive pathogenesis. Further, the intestinal microbiota characteristics related to MDD, the main regulatory pathways, and the potential efficacy of microbiome-targeted intervention measures-including psychobiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary strategies-were sorted out. In the clinical assessment and drug research of depression, the assessment tools are mainly divided into two categories: clinician-rated and self-reported. These two types are often used together to provide multi-dimensional evidence of therapeutic efficacy. Evidence suggests that stress-related intestinal permeability may initiate gut dysbiosis, which in turn can impair barrier function, promote neuroinflammation, disrupt neurotransmitter synthesis, and overactivate the HPA axis, potentially exacerbating depressive symptoms. Interventions targeting the gut microbiota may help reshape microbial communities, increase short-chain fatty acids (SCFAs) and 5-Hydroxytryptamine (5-HT), and dampen inflammatory and stress responses, thereby offering a promising, non-pharmacological avenue for alleviating MDD. This review not only offers a theoretical foundation for microbiota-based therapeutics in MDD but also highlights pathways toward developing safe, effective non-pharmacological strategies for depression management.

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Gut microbiota dysbiosis and depression: Bidirectional interactions, mediating pathways, and microecological therapeutics

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