Fig. 10

Inhibition of abnormal synaptic pruning is the key to targeting microbes to treat depression. Gut microbiota contributes to regulating the gut-brain axis and maintaining health, while its alteration (increase of Proteobacteria and decreased of microbial diversity) due to CUMS is related to depression and its adverse consequences on cognition. XYS supplementation is thought to decrease Proteobacteria and regulated the composition and metabolism of gut microbiota (1), thereby, contribute to gut barrier function and immune homeostasis (2); this attenuates the translocation of components of Gram-negative bacteria (3), which decreases the peripheral inflammatory tone and inhibits activation of C3/CR3 (4) and microglia-mediated abnormal synaptic pruning in the CNS (5). Therefore, the supplement of XYS beneficially impacts on depression, via restoration of gut microbiota and its regulatory role in the gut-brain axis, suggesting that inhibition of abnormal synaptic pruning is the key to targeting microbes to treat depression