Characterizing the role of the gut microbiota-inflammation-brain axis in major depressive disorder: an integrative multi-omics study.

BACKGROUND: Gut microbial dysbiosis and inflammation have been implicated in the pathophysiology of major depressive disorder (MDD). However, no attempts have been made to comprehensively investigate the potential relationship between gut microbiota, inflammation, brain function, and clinical features in MDD. METHODS: We conducted an integrative multi-omics study to examine the multi-dimensional differences in gut microbiome, inflammatory cytokines, brain functional connectivity, and clinical features between 60 MDD patients and 70 healthy controls. Furthermore, the potential associations between these multi-omics alterations were assessed using correlation and serial mediation analyses. RESULTS: MDD patients exhibited both depleted beneficial gut microbes and enriched detrimental bacteria, elevated interleukin-1 beta (IL-1β) level, a mix of decreased and increased functional connectivity of multiple brain regions. More important, we found that decreased abundance of anti-inflammatory bacterium (i.e., Blautia) led to increased IL-1β level, which in turn resulted in functional abnormalities in fronto-parietal regions that were associated with clinical symptoms and executive dysfunction. CONCLUSION: Our findings may corroborate the gut microbiota-inflammation-brain axis hypothesis in depression, as well as highlight the potential use of targeting gut microbiota as anti-inflammatory intervention strategies in the prevention or treatment for MDD patients.