Our findings suggest that DRD2 deficiency underlies pituitary adenoma dependent on Escherichia coli translocation from the gut and activating microglia GSDMD/ HMGB1/MAPK pathway, and provide a novel preclinical rationale for antimicrobial agents, microglial depletion, or HMGB1 inhibitor ethyl pyruvate for the treatment of pituitary adenoma. Here, DRD2 is linked to pituitary gland adenoma.