Mycobacterium avium subspecies paratuberculosis—An environmental trigger of type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is an autoimmune disease. The etiology of T1DM is incompletely understood but environmental agent(s) are thought to trigger T1DM in the genetically at-risk. Humans are widely exposed to Mycobacterium avium subspecies paratuberculosis (MAP), a proven multi-host chronic enteric pathogen that is mostly studied in ruminant animals and causes the inflammatory disease paratuberculosis or Johne’s disease. In humans, MAP is the putative cause of Crohn’s disease and has been linked to sarcoidosis, autoimmune thyroiditis, multiple sclerosis and autoimmune diabetes. The role of MAP as a trigger for T1DM was first postulated in 2005; subsequent studies suggest a link. This article discusses MAP, human exposure to MAP, genetic susceptibility to MAP and MAP in human disease including T1DM.

~ Coad Thomas Dow.
Vol.2, No.1, 88-95 (2012) Journal of Diabetes Mellitus | doi:10.4236/jdm.2012.21014
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Paratuberculosis and Type I diabetes – Is this the trigger?

Type 1 diabetes mellitus (T1DM) is an autoimmune disease. The etiology of T1DM is incompletely understood but environmental agent(s) are thought to trigger T1DM in the genetically at risk. Exposure to cow’s milk early in life is a recognized risk factor in the development of T1DM. Mycobacterium avium ss. paratuberculosis (MAP) is the cause of bovine Johne’s disease and also is thought to act as an immune antigen in Crohn’s disease and other granulomatous diseases. MAP is shed in cow’s milk and has been shown to survive pasteurization. Geneticsusceptibilities, epitope homologies and epidemiologic studies are presented that support MAP as a causative agent of T1DM in the genetically at risk.

~ Dow CT.
Med Hypotheses. 2006;67(4):782-5. Epub 2006 Jul 7.
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Cows, Crohn’s and more: Is Mycobacterium paratuberculosis a superantigen?

The plausibility of a causal role of Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn’s disease has gone from controversial to compelling. This century old debate is resolving because of unfolding understanding of shared genetic susceptibilities for Crohn’s and mycobacterial infection in addition to newer laboratory tests to detect MAP which have linked MAP and Crohn’s. Mycobacterial heat shock proteins are associated with a multitude of ‘‘autoimmune’’ diseases, including Type 1 diabetes mellitus (T1DM) and the initiating events of atherosclerosis. These heat shock proteins may come from MAP; this article postulates a causal role for MAP in multiple inflammatory and ‘‘autoimmune’’ diseases.

~Thomas Dow C.
Med Hypotheses. 2008 Dec;71(6):858-61. Epub 2008 Sep 11.
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Detection of Mycobacterium avium ss. Paratuberculosis in Blau Syndrome Tissues

Background and Aim of the Work:  Blau syndrome is an inherited granulomatous inflammatory disorder with clinical findings of uveitis, arthritis, and dermatitis. Although rare, Blau syndrome shares features with the more common diseases sarcoidosis and Crohn’s disease. The clinical findings of Blau syndrome are indistinguishable from juvenile sarcoidosis; the mutations of Blau syndrome are on the same gene of chromosome 16 (CARD15) that confers susceptibility to Crohn’s disease. The product of this gene is part of the innate immune system.  Mycobacterium avium ss. paratuberculosis (MAP) is the putative cause of Crohn’s disease and has been implicated as a causative agent of sarcoidosis. Methods. Archival tissues of individuals with Blau syndrome were tested for the presence of MAP. Results. DNA evidence of MAP was detected in all of the tissues. Conclusions. This article finds that MAP is present in Blau syndrome tissue and postulates that it has a causal role. The presence of MAP in Blau syndrome—an autosomal dominant, systemic inflammatory disease—connects genetic and environmental aspects of “autoimmune” disease.

~Dow CT, Ellingson JL.
Autoimmune Dis. 2010 Jun 20;2010:127692.
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Molecular identification of Mycobacterium avium subspecies paratuberculosis in an Italian patient with Hashimoto’s thyroiditis and Melkersson–Rosenthal syndrome

To the best of our knowledge, this report is the first observation of a MAP infection in a patient with MRS. The findings are consistent with early exposure to dietary cows’ milk and underline the possibility that milk from cattle with Johne’s disease could be a potential transmission vehicle for MAP to humans.

~D’Amore M, Lisi S, Sisto M, Cucci L, Dow CT.
J Med Microbiol. 2010 Jan;59(Pt 1):137-9. Epub .
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Proposing a relationship between Mycobacterium avium subspecies paratuberculosis infection and Hashimoto’s thyroiditis

Humans are widely exposed to Mycobacterium avium subspecies paratuberculosis (MAP), a proven multi-host chronic enteric pathogen that has recently been linked to autoimmune diabetes. In the present study we used a MAP speciesspecific polymerase chain reaction with the insertion element IS900-specifi c probe to detect MAP infection in members of the same family suffering from Hashimoto’s thyroiditis.

~Sisto M, Cucci L, D’Amore M, Dow TC, Mitolo V, Lisi S.
Scand J Infect Dis. 2010 Oct;42(10):787-90.
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