Eucommiae cortex Polysaccharides Ameliorate the Chronic Unpredictable Mild Stress-induced Depression-related Gut Dysbiosis and Neuroinflammation in Mice

Polysaccharides have a significant role in fostering the growth of enteric probiotics, improving immune function, and regulating the microecology of the gut. Recent studies suggest that gut microbiota affects the onset and progression of depression through the gut-brain axis. Eucommiae cortex polysaccharides (EPs) exhibit the potential in regulating gut microbiota. In the present study, chronic unpredictable mild stress (CUMS) mice model was used to investigate the beneficial effects of EPs on depression. Our results showed that EPs ameliorated depressive and anxiety-like behaviors induced by CUMS, especially enhancing the density of dopamine-positive cells. Meanwhile, oral EPs remodelled gut dysbiosis and inhibited colitis, thereby meliorating pro-inflammatory responses in microglia by inhibiting TLR4/NFKB/MAPK signaling pathways and preventing the adult neurogenesis disorders in CUMS mice. Furthermore, correlation analysis showed a strong correlation between depressive traits and perturbed gut microbiota. Therefore, oral EPs might be a promising nutritional strategy to treat CUMS-induced depression via regulating the gut-brain axis.