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BCG, Autoimmune Diabetes and M. Paratuberculosis
Coad Thomas Dow*
Mc Pherson Eye Research Institute, University of Wisconsin, Madison, USA

Article
The recent NPJ Vaccine journal included an article by Kuhtreiber, et al. [1], wherein the authors reported that attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) given to individuals with autoimmune diabetes (T1DM) resulted in improved control of blood sugars. In a randomized 8-year study diabetics with long-term disease were given two doses of the BCG vaccine; at year three, the intervention group had lowered hemoglobin A1c to near normal levels and this was maintained for the next five years.

BCG, one of the oldest vaccines, was developed for Tuberculosis (TB) protection. Beyond infectious disease, BCG has immuno-stimulating properties that have made it standard therapy for bladder cancer [2].

There is a body of work that links Mycobacterium Avium ss. Paratuberculosis (MAP) to T1DM along with a number of other inflammatory/autoimmune diseases [3-8]. It purports that shared genetic risk for both mycobacterial infection and T1DM offers a permissive environ for latent MAP infection; and that MAP’s immunodominant Heat Shock Protein 65 (HSP65) cross reacts with pancreatic Glutamic Acid Decarboxylase (GAD) through molecular mimicry [8] resulting in anti-GAD antibodies causing an immune mediated destruction of insulin producing islet cells of the pancreas. Humans are mostly exposed to MAP via food from infected animals [9].

The genus Mycobacterium includes important pathologic infectious agents causing human and animal diseases. The M. tuberculosis complex causes TB in humans and cattle. M. leprae causes human leprosy. MAP causes Paratuberculosis in ruminant animals and is the putative cause of Crohn’s disease in humans; it is also associated with T1DM, sarcoidosis, Blau syndrome, multiple sclerosis and autoimmune (Hashimoto’s) thyroiditis [6]. Other Mycobacterium species are deemed “environmental” [10]. Interestingly, BCG has also been used to vaccinate against M. leprae infection-leprosy [11].

This correspondence suggests an alternative explanation: The favorable outcome of the Kuhtreiber study was due to BCG curtailing MAP allowing recovery of pancreatic function. Further information on this topic is available on this podcast: https://www.youtube.com/watch?v=1Mf7KtDquyM.
Conflict of Interest
I declare potential competing interests in the material discussed in the correspondence as I have an investment interest in Paralab, LLC and MAP/PATH, LLC. Both companies were formed to advance treatments for MAP infections.

References
  1. Kuhtreier WM, Tran L, Kim T, Dybala M, Nguyen B, et al. (2018) Long-term reduction in hyperglycemia in advanced type 1 diabetes: The value of induced aerobic glycolysis with BCG vaccinations. npj Vaccines 3: 1-14.
  2. Zheng YQ, Naguib YW, Dong Y, Shi YC, Bou S, et al. (2015) Applications of bacillus calmette-guerin and recombinant bacillus calmette-guerin in vaccine development and tumor immunotherapy. Expert Rev Vaccines 14: 1255-1275.
  3. Dow CT (2006) Paratuberculosis and type 1 diabetes: Is this the trigger? Med Hypotheses 67: 782-785.
  4. Masala S, Cossu D, Piccinini S, Rapini N, Massimi A, et al. (2014) Recognition of zinc transporter 8 and MAP3865c homologous epitopes by new-onset type 1 diabetes children from continental Italy. Acta Diabetol 51: 577-585.
  5. Hesam Shariati S, Alaei A, Keshavarz R, Mosavari N, Rabbani A, et al. (2016) Detection of Mycobacterium Avium subsp. Paratuberculosis in Iranian patients with type 1 diabetes mellitus by PCR and ELISA. J Infect Dev Ctries 10: 857-862.
  6. Sechi LA, Dow CT (2015) Mycobacterium Avium ss. Paratuberculosis zoonosis-The hundred year war-beyond crohn’s disease. Front Immunol 6: 96.
  7. Dow CT (2018) Failure of TRIGR study opens door to alternative explanation of T1DM etiopathology. J Diabetes Metab 9: 112.
  8. Dow CT (2012) M. Paratuberculosis heat shock protein 65 and human diseases: Bridging infection and autoimmunity. Autoimmune Dis.
  9. National Advisory Committee on Microbiological Criteria for Foods (2010) Assessment of food as a source of exposure to Mycobacterium Avium subspecies Paratuberculosis (MAP). J Food Prot 73: 1357-1397.
  10. Frothingham R (1999) Evolutionary bottlenecks in the agents of tuberculosis, leprosy, and Paratuberculosis. Med Hypotheses 52: 95-99.
  11. Merle CS, Cunha SS, Rodrigues LC (2010) BCG vaccination and leprosy protection: Review of current evidence and status of BCG in leprosy control. Expert Rev Vaccines 9: 209-222.

Citation: Dow CT (2018) BCG, Autoimmune Diabetes and M. Paratuberculosis. J Diabetes Metab Disord 5: 024.
Copyright: © 2018 Dow CT, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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