Mycobacterium are among the oldest co-evolutionary partners of humans. The attenuated Mycobacterium bovis Bacillus Calmette Guérin (BCG) strain has been administered globally for 100 years as a vaccine against tuberculosis. BCG also shows promise as treatment for numerous inflammatory and autoimmune diseases. Here, we report on a randomized 8-year long prospective examination of type 1 diabetic subjects with long-term disease who received two doses of the BCG vaccine. After year 3, BCG lowered hemoglobin A1c to near normal levels for the next 5 years. The BCG impact on blood sugars appeared to be driven by a novel systemic and blood sugar lowering mechanism in diabetes. We observe a systemic shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis, a state of high glucose utilization. Confirmation is gained by metabolomics, mRNAseq, and functional assays of cellular glucose uptake after BCG vaccinations. To prove BCG could induce a systemic change to promote accelerated glucose utilization and impact blood sugars, murine data demonstrated reduced blood sugars and aerobic induction in non-autoimmune mice made chemically diabetic. BCG via epigenetics also resets six central T-regulatory genes for genetic re-programming of tolerance. These findings set the stage for further testing of a known safe vaccine therapy for improved blood sugar control through changes in metabolism and durability with epigenetic changes even in advanced Type 1 diabetes.
A news report about this paper was posted to Steve Gibson’s grc.health news group. Although it has this undercurrent of “auto-immunity”, it doesn’t really seem to be about that. Or at least not in the typical sense one sees the immune system invoked.
This appears actually to be a metabolic hack that involves triggering a set of immune cells in the blood of T1D patients given the vaccine to use glycolysis non-aerobically in non-hypoxic conditions. That is, “aerobic glycolysis”. These cells then apparently become a sink for sugar, fermenting it to lactic acid or otherwise shunting it off into other pathways. As a result the T1D patents given these vaccinations dropped their A1C’s from 7 to 6.
A few oddities about this process. (1) the drop in A1C occurs 2-3 years after the vaccinations but then seems durable – still in effect 5 years later and (2) it doesn’t impact the production of insulin by the pancreases of the patients. The patients are still diabetic, they just have better blood sugar control.
If you go into the paper understanding that it really is a metabolic hack that causes the drop in A1C’s it is much easier to understand. That said, BCG vaccination has also been used to treat a type of bladder cancer and multiple sclerosis. The latter presumably must be through actual immuno-modulation, right?
Super interesting. Thanks for posting this.
Yes, you are welcome. Actually I haven’t been able to find any other person who found this interesting. No one I’ve told at work (largely research biology professors) nor anywhere else. Just more indication to me of how weird biology is. Always something coming out of left field to surprise you. Also the fact that these guys did an 8 year study when the end point they were looking for (restoration of pancreatic islet function) never happens. But they doggedly must have persevered tracking down the source of the 1 point drop in A1C that they did see.