The L. plantarum WLPL04 can rescue anxiety/depressive-like behaviors and cognitive dysfunctions, reverse the abnormal change in intestinal microbiota, and alleviate the reduced levels of 5-HT, BDNF, and TrkB induced by chronic stress in mice, providing an experimental basis for the therapeutic application of L. plantarum on anxiety/depression. Here, BDNF is linked to major depressive disorder.