Possibly, SGKL improves behaviors in CRS‐induced rats targeting PI3k/Akt/mTOR pathway via two pathways: a) SGKL alters the composition structure of gut microbiota to target the PI3K/Akt/mTOR pathway in the brain, thereby regulating depression progression; b) transported by the circulatory system, SGKL may be delivered to microglia and then target PI3K/Akt/mTOR pathway‐mediated microglial activation and inflammation. The gene discussed is SGK3; the disease is major depressive disorder.