Nearly 100 years after it was developed, the Calmette-Guerin (perhaps better known as the BCG) vaccine continues to astonish scientists with its far-reaching impact on the human immune system. In the latest research, a team from the Massachusetts General Hospital Immunobiology Laboratory show how exposure to the bacteria in the vaccine can restore normal blood sugar levels in patients with type 1 diabetes (T1D) by boosting the appetite of white blood cells.
The as-of-yet unpublished insights, set to be presented today at the European Association for the Study of Diabetes 2018 Annual Meeting, build upon previous work suggesting that one contributing cause of T1D – an autoimmune disease wherein the body attacks its own insulin-producing cells – may be insufficient exposure to things the immune system is actually meant to target.
"It has long been believed that the move to cleaner and more urban environments is involved in not only how type 1 diabetes develops, but increased incidence of the disease," lead author Dr Denise Faustman said in a statement.
"In particular, reduced exposures to certain microbes, the consequence of better sanitation, greater use of antibiotics, smaller family sizes, cleaner houses, less daily exposures to the soil, and less exposure to domesticated animals, appears to have changed the modern metabolic function."
The BCG vaccine, which protects against tuberculosis by introducing a harmless, weakened lineage of bacteria closely related to Mycobacterium tuberculosis, has been shown to have the unintended but incredibly beneficial side effect of jumpstarting the human immune system as a whole. Past research has shown that BCG can help people fight a variety of conditions, including many types of cancers and parasitic infections.
Based on evidence that BCG is also beneficial for mitigating autoimmune disorders, Dr Faustman’s group initiated a small clinical trial wherein adults with T1D were given two BCG vaccines four weeks apart or two placebo shots. Four years later, the vaccinated subjects’ (n=9) average blood sugar level had dropped by over 18 percent, nearly back to non-disease levels, without inducing episodes of hypoglycemia.
A study published in June reported that subjects maintained these reductions during four additional years of follow-up, during which time placebo subjects’ average blood sugar score continued to rise. Using blood samples collected from these subjects and 230 additional T1D and control subjects, Dr Faustman and her team were also able to pinpoint the epigenetic mechanism underlying the vaccine’s effect: It appears that BCG causes cells to switch from the favored glucose to ATP pathway, oxidative phosphorylation, to a less efficient process called aerobic glycolysis, thus helping to consume the glucose lingering in the bloodstream due to a lack of insulin.
And the team’s newest findings reveal another part of this immune-metabolism puzzle, namely that T1D patients’ white blood cells consume less blood glucose than those from non-diabetics. The rate is similar to that seem in patients with less microbial exposure early in life.
"BCG is an organism that needs a lot of energy sources. It lives inside white blood cells and elevates the sugar utilization", explains Dr Faustman.
"The BGC vaccinations[,] like tuberculosis itself, convert a depressed lymphatic system deficient in sugar utilization into a highly efficient process, a restoration similar to normal subjects without diabetes."
Her team concludes that their discoveries will pave the way for additional, larger studies of the BCG vaccine for treatment of T1D.