BCG Therapy for Type 1 Diabetes: Restoration of Balanced Immunity and Metabolism.

The bacillus Calmette-Guerin (BCG) vaccine is a microorganism developed as a vaccine for tuberculosis 100 years ago and used as therapy for bladder cancer 40 years ago. More recently, BCG has shown therapeutic promise for type 1 diabetes (T1D) and several other autoimmune diseases. In T1D, BCG restored blood sugars to near normal, even in patients with advanced disease of >20 years duration. This clinically important effect may be driven by resetting of the immune system and the shifting of glucose metabolism from overactive oxidative phosphorylation, a state of minimal sugar utilization, to aerobic glycolysis, a state of high glucose utilization, for energy production. The mechanistic findings support the Hygiene Hypothesis and reveal the immune and metabolic synergy of mycobacterial reintroduction in modern humans.