We inferred that SGKL treatment might activate the PI3K/Akt/mTOR pathway that mediates the regulation of gut microbiota alteration toward microglia to evoke metabolic reprogramming and NMDAR‐associated neurobiology MDD at the molecular level, which is required for a follow‐up work based on fecal microbiota transplantation. The gene discussed is AKT1; the disease is major depressive disorder.