Interaction of the gut microbiota and brain functional connectivity in late-life depression.

Background: Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD).

Methods: We performed fecal 16S ribosomal RNA (rRNA) sequencing and resting-state functional magnetic resonance imaging in a case-control cohort of older adults with LLD and healthy controls to characterize the association between gut microbiota and brain functional connectivity (FC). We used the Hamilton Depression Rating Scale (HAMD) to assess depressive symptoms.

Results: We included 32 adults with LLD and 16 healthy controls. At the genus level, the relative abundance of Enterobacter, Akkermansiaceae, Hemophilus, Burkholderia, and Rothia was significantly higher among patients with LDD than controls. Reduced FC within mood regulation circuits was mainly found in the frontal cortex (e.g., the right superior and inferior frontal gyrus, right lateral occipital cortex, left middle frontal gyrus, and left caudate) among patients with MDD. Group-characterized gut microbes among controls and patients showed opposite correlations with seed-based FC, which may account for the aberrant emotion regulation among patients with LDD. The abundance of Enterobacter (dominant genus among patients with LLD) was positively correlated with both HAMD scores (r = 0.49, p = 0.0004) and group-characterized FC (r = -0.37, p < 0.05), while Odoribacter (dominant genus among controls) was negatively correlated with both HAMD scores (r = -0.30, p = 0.04) and group-characterized FC.

Limitations: The study's cross-sectional design and small sample size limit causal inferences; larger longitudinal studies are required for detailed subgroup analyses.

Conclusion: We identified significant correlations between LDD-characterized gut microbes and brain FC, as well as depression severity, which may contribute to the pathophysiology of depression development among patients with LLD. Specific microbes were linked to altered brain connectivity, suggesting potential targets for treating LLD.