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.