The Gut–Brain Axis in Depression: A Systematic Review of Microbiota and Mental Health

Abstract

Major depressive disorder (MDD) affects approximately 280 million people worldwide, yet conventional pharmacotherapy achieves remission in only 30–50% of patients, intensifying the search for novel biological substrates. This systematic review, conducted according to PRISMA 2020 guidelines across six electronic databases (2014–March 2025), synthesised 89 studies examining gut microbiota composition in adults with MDD compared to healthy controls. MDD was consistently associated with reduced alpha diversity and a recurrent dysbiotic pattern, herein proposed as a depressive dysbiosis signature, characterised by depletion of butyrate-producing genera (Faecalibacterium, Roseburia, Eubacterium, Coprococcus) and enrichment of pro-inflammatory taxa (Alistipes, Eggerthella, Streptococcus). While this pattern was observed across multiple cohorts, significant inter-study heterogeneity precludes its definition as a universal microbial signature for MDD. Beta diversity analyses demonstrated robust compositional separation between cohorts. Plausible mechanistic pathways included compromised short-chain fatty acid production, increased intestinal permeability, low-grade systemic inflammation, tryptophan shunting toward the kynurenine pathway, and hypothalamic–pituitary–adrenal axis dysregulation. Preclinical faecal microbiota transplantation provided translational evidence consistent with a causal interpretation, while randomised probiotic trials demonstrated significant reductions in depressive symptom severity compared with placebo. Probiotic effects are strain-specific according to ISAPP consensus; generalisation across strains is not warranted. Gut microbiota dysbiosis represents a biologically plausible mediator of depression pathophysiology, with a recurrent dysbiotic pattern, characterised by depletion of butyrate-producing taxa and enrichment of pro-inflammatory genera, showing emerging diagnostic and therapeutic potential.