The association between gut microbiota and functional connectivity in cognitive impairment of first-episode major depressive disorder

The pathogenesis of major depressive disorder(MDD) and cognitive impairment has been linked to gut microbiota; however, the relationship between cognitive impairment and gut microbiota in patients with MDD and their underlying mechanisms remain unclear. This study aimed to investigate the brain-gut axis involved in cognitive impairment among patients with first-episode MDD through neuroimaging and microbiome analyses. 43 microbial species were different between patients with first-episode MDD and healthy controls. Notably, the relative abundances of Amycolatopsis sp. Hca4 and Shewanella livingstonensis were lower in patients with MDD compared to healthy controls, with Amycolatopsis sp. Hca4 negatively correlated with processing speed and Shewanella livingstonensis positively correlated with verbal learning. Brain network analysis revealed significant connectivity between subnetworks in patients with MDD, with cognitive function closely associated with connections between somatomotor-limbic, default mode-limbic and frontoparietal-limbic networks. Additionally, Amycolatopsis sp. Hca4 was found to modulate the relationship between the functional connectivity of the middle frontal gyrus and parahippocampal gyrus and working memory, with this correlation varying according to the abundance of Amycolatopsis sp. Hca4. These findings suggest that gut microbiota disturbances in patients with first-episode MDD serve as a regulatory factor for brain dysfunction and cognitive impairment.