Bacillus Calmette-Guerin 's beneficial impact on glucose metabolism: evidence for broad based applications

Gabriella F Shpilsky; Hiroyuki Takahashi; Anna Aristarkhova; Michele Weil; Nathan Ng; Kacie J Nelson; Amanda Lee; Hui Zheng; Willem M Kühtreiber; Denise L Faustman

doi:10.1016/j.isci.2021.103150

Bacillus Calmette-Guerin 's beneficial impact on glucose metabolism: evidence for broad based applications

iScience. 2021 Sep 21;24(10):103150. doi: 10.1016/j.isci.2021.103150. eCollection 2021 Oct 22.

Authors

Affiliations

¹ Massachusetts General Hospital, Immunobiology Laboratories, Boston, MA 02129, USA.
² Massachusetts General Hospital, Diabetes Unit, Boston, MA 02129, USA.
³ Massachusetts General Hospital and Harvard Medical School, Statistics Department, Boston, MA 02129, USA.
⁴ Massachusetts General Hospital and Harvard Medical School, Immunobiology Laboratories, Boston, MA 02129, USA.

Abstract

Bacillus Calmette-Guerin (BCG) vaccinations improve glycemic control in juvenile-onset Type I diabetes (T1D), an effect driven by restored sugar transport through aerobic glycolysis. In a pilot clinical trial, T1D, but not latent autoimmune diabetes of adults (LADA), exhibited lower blood sugars after multidose BCG. Using a glucose transport assay, monocytes from T1D subjects showed a large stimulation index with BCG exposures; LADA subjects showed minimal BCG-induced sugar responsiveness. Monocytes from T1D, type 2 diabetes (T2D), and non-diabetic controls (NDC) were all responsive in vitro to BCG by augmented sugar utilization. Adults with prior neonatal BCG vaccination show accelerated glucose transport decades later. Finally, in vivo experiments with the NOD mouse (a T1D model) and obese db/db mice (a T2D model) confirm BCG's blood-sugar-lowering and accelerated glucose metabolism with sufficient dosing. Our results suggest that BCG's benefits for glucose metabolism may be broadly applicable to T1D and T2D, but less to LADA.

Keywords: Human metabolism; Immunology.