One water-soluble of polysaccharide from Ginkgo biloba leaves with antidepressant activities via modulation of the gut microbiome

Depression, a mental illness characterized by persistent feeling of sadness and loss of interest has been a serious health problem worldwide. Manipulation of the microbiota by probiotics and prebiotics represents a novel emerging strategy for the treatment of various psychiatric illness such as major depressive disorders. Here, here we show that one water-soluble polysaccharide from Ginkgo biloba leaves (GPS) reduced stress-induced depression and reversed gut dysbiosis. Similar to the antidepressant paroxetine, GPS significantly reduced the immobility times in the tail suspension test (TST) and forced swimming test (FST) and anxiety-like behavior in open field test (OFT). Consistent with the improvement of depression-like behavior above, GPS mice had elevated serotonin and dopamine levels in multiple brain regions including hippocampus, cerebral cortex and olfactory bulb, relative to PBS unpredictable chronic mild stress treatment (UCMS) mice. GPS treatment could rescue the stress-induced reduction in the density of serotonin-positive and dopamine-positive cells. Fecal microbiome transplant (FMT) combined with antibiotic treatment showed that the anti-depressant activity of GPS had a causal relationship with intestinal microbes. By performing a pyrosequencing-based analysis of bacterial 16S rRNA (V3+V4 region) in fecal, the results showed that GPS reversed depression-associated gut dysbiosis and increased richness of Lactobacillus species which has been proven to be a path to relieve depression. Our results demonstrated that polysaccharide from Ginkgo biloba leaves might be a promising pharmacotherapeutics candidate for treating depression.