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

Efficacy of Gut Microbiota-Targeted Interventions for Major Depressive Disorder: A Systematic Review and Network Meta-Analysis.

Reproducible Gut Microbiome Alterations in Major Depressive Disorder: A Systematic Review of Taxonomic and Functional Findings

Background/Objectives: Major depressive disorder (MDD) has been increasingly associated with alterations of the gut microbiome through the microbiota–gut–brain axis. However, published findings remain highly heterogeneous, limiting identification of reproducible microbial signatures associated with depression. This systematic review aimed to evaluate reproducible taxonomic and functional gut microbiome alterations in patients with MDD compared with healthy controls. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science Core Collection, and the Cochrane Library for studies published between January 2016 and December 2025. Observational human studies evaluating gut microbiome composition in adults with clinically diagnosed MDD and healthy control groups were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Due to substantial methodological heterogeneity, findings were synthesized using structured qualitative narrative analysis. Results: Sixteen observational studies were included in the qualitative synthesis. Findings related to alpha diversity were inconsistent across studies, whereas beta diversity alterations demonstrated greater reproducibility across independent cohorts. The most recurrent microbiome pattern involved depletion of short-chain fatty acid (SCFA)-producing bacteria, particularly Faecalibacterium and Roseburia, together with recurrent alterations affecting members of the Ruminococcaceae, Lachnospiraceae, and Clostridia groups. Functional microbiome alterations demonstrated greater consistency than higher-level taxonomic findings and included reduced butyrate synthesis pathways, dysregulated amino acid and tryptophan metabolism, increased lipopolysaccharide biosynthesis, and enrichment of pro-inflammatory microbial signatures. Antidepressant-naïve cohorts generally demonstrated more homogeneous dysbiosis patterns than mixed-treated populations. Conclusions: Current evidence suggests that functional gut microbiome dysregulation may represent a more reproducible biological feature of MDD than isolated taxonomic alterations alone. However, substantial heterogeneity in study design, participant characteristics, sequencing methodologies, and analytical approaches continues to limit clinical translation. Large-scale longitudinal multi-omics studies using standardized methodologies are required to clarify the role of the gut microbiome in depressive disorders and to evaluate the potential utility of microbiome-based biomarkers and interventions in mental health and public health practice.

Gut microbial biomarkers for major depressive disorder: a cross-sectional study

Background Alterations in the gut microbiota have been associated with a variety of psychiatric disorders, including major depressive disorder (MDD). However, the relationship between MDD and gut microbial communities remains incompletely understood. Most previous studies have primarily focused on gut bacteria, with relatively limited attention to other microbial components. Methods In this study, we analyzed gut microbial profiles from 36 patients with MDD and 36 healthy controls using metagenomic sequencing data. The MaAsLin2 algorithm was applied to identify potential microbial biomarkers associated with MDD. Results A total of 6 bacterial biomarkers and 7 viral biomarkers were identified. The models based on these features demonstrated strong predictive performance, with area under the curve (AUC) values of 0.891 for bacteria and 0.878 for viruses. Notably, the combined bacterial-viral model achieved an AUC of 0.946. These findings were further evaluated through external testing in two unrelated research cohorts. In the Shanxi cohort, the AUC values were 0.825 (bacteria), 0.803 (viruses), and 0.972 (combined model). In the Wuhan cohort, the AUC values were 0.683 (bacteria), 0.693 (viruses), and 0.784 (combined model). Conclusion In summary, our results highlight the potential of gut bacterial and viral biomarkers as candidate biomarkers and potential auxiliary tools for MDD assessment and suggest that integrating multi-domain microbial features may improve prediction accuracy.

Gut microbiome variability and brain structure and function in unipolar and bipolar depression: A review.

INTRODUCTION Depression is a multifactorial disorder with significant global health impact. Neuroimaging advances have provided insights into neural mechanisms underlying depression, while gut microbiome alterations have been linked to brain structure and function. This review summarizes evidence on the association between gut microbiome variability and brain structural and functional changes in Major Depressive Disorder (MDD) and Bipolar Depression (BD). METHODS A bibliographic search was conducted on PubMed, Scopus and Web of Science for original studies investigating correlations between gut microbiome and brain structure and function. RESULTS Three studies investigated probiotic interventions in MDD, showing significant associations with increased gray matter volume (GMV) in the calcarine sulcus, reduced putamen and hippocampal activation, and altered fronto-limbic functional connectivity, especially within the precuneus and superior parietal lobule. Also, observational studies in MDD showed that specific microbial taxa or alpha diversity were positively correlated with limbic and basal ganglia GMV, whereas other taxa negatively correlated with frontal connectivity or GMV in regions involved in memory, somatosensory integration, and emotional regulation. Finally, although no interventional studies were available for BD, the available observational studies in this disorder exhibited gut-brain imbalance associations with immune activation and prefrontal dysfunction, with gut microbes linked to neuroactive metabolites correlated with altered connectivity in thalamus, striatum, and language and limbic regions. CONCLUSIONS From the available literature emerged that gut microbiome variations seem to be associated with brain structural and functional alterations in both MDD and BD, with preliminary evidence also suggesting significant neurobiological effects of probiotics in MDD. Nonetheless, further studies are needed to confirm the role of gut microbiome modulation as part of personalized approaches.

Gut Microbiome in Depression with and without REM Sleep Behavior Disorder.

Gut microbiome provides a candidate approach for potential risk stratification in psychiatric populations, and MDD + RBD may represent a biologically distinct depression subtype associated with potential neurodegenerative risk.

Gut Microbiota and Metabolites: Orchestrating Depression Pathogenesis Through the Microbiota–Gut–Brain Axis’s Neural, Immune, and Metabolic Routes

Depression (major depressive disorder, MDD) is a globally prevalent, highly disabling, and complex mental disorder whose pathogenesis has not been fully elucidated. In recent years, the role of the gut microbiota in depression via the “microbiota–gut–brain axis” (MGB axis) has attracted increasing attention. A large body of evidence indicates that the gut microbiota and its metabolites can engage in bidirectional communication with the central nervous system through three core pathways—neural, immune, and metabolic—thereby profoundly influencing the onset and progression of depression. This article reviews the specific mechanisms by which the gut microbiota affects depression through the aforementioned pathways, including regulating the balance of neurotransmitters (e.g., GABA and 5-HT), mediating neuroinflammatory responses, and adjusting the levels of metabolites such as short-chain fatty acids. This study aims to provide a theoretical basis for an in-depth understanding of the pathophysiological mechanisms of depression and the development of novel microbiota-based intervention therapeutic strategies.