Differences in gut microbiota correlate with symptoms and regional brain volumes in patients with late-life depression

Depression is associated with gut dysbiosis that disrupts a gut-brain bidirectional axis. Gray matter volume changes in cortical and subcortical structures, including prefrontal regions and the hippocampus, have also been noted in depressive disorders. However, the link between gut microbiota and brain structures in depressed patients remains elusive. Neuropsychiatric measures, stool samples, and structural brain images were collected from 36 patients with late-life depression (LLD) and 17 healthy controls. 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities for quantitation of microbial composition, abundance, and diversity. T1-weighted brain images were assessed with voxel-based morphometry to detect alterations in gray matter volume between groups. Correlation analysis was performed to identify the possible association between depressive symptoms, brain structures and gut microbiota. We found a significant difference in the gut microbial composition between patients with late-life depression (LLD) and healthy controls. The genera Enterobacter and Burkholderia were positively correlated with depressive symptoms and negatively correlated with brain structural signatures in regions associated with memory, somatosensory integration, and emotional processing/cognition/regulation. Our study purports the microbiota-gut-brain axis as a potential mechanism mediating the symptomatology of LLD patients, which may facilitate the development of therapeutic strategies targeting gut microbes in the treatment of elderly depressed patients.