Journal of Diabetology (Jan 2023)

Role of Mycobacterium paratuberculosis infection in etiopathogenesis of type 1 diabetes: A review of population-based studies

  • Ashish Gautam,
  • Shoor Vir Singh,
  • Saurabh Gupta,
  • Nikhil Pursnani,
  • Prabhat Agrawal

DOI
https://doi.org/10.4103/jod.jod_78_23
Journal volume & issue
Vol. 14, no. 4
pp. 193 – 197

Abstract

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Introduction: Multiple mechanisms were proposed for the etiopathogenesis of type 1 diabetes mellitus (T1DM). An interplay between genetic, environmental, and immunological factors leads to generate autoantibodies against glutamic acid decarboxylase 65, intracellular adhesion (ICA)-512, and insulin autoantibodies (IAA) proteins of beta cells. Molecular mimicry is the best proposed mechanism of the above, but yet needs much solid evidence. Zinc transporter 8 (ZnT8) and proinsulin (PI) proteins of beta cells act as epitopes for some partially recognized proteins (MAP3865c, MAP1, 4αgbp, and MAP2404c) of mycobacterium paratuberculosis (MAP) generating autoantibodies against them. Similarly, other protein molecular mimickers were also reported. This review collects the latest evidence for the environmental etiopathogenesis of T1DM pertaining to MAP at the background of the phenomenon of molecular mimicry, and it proposes more directions for research in the field. Materials and Methods: Using the keywords “MAP and T1DM,” “MAP and zoonotic diseases,” T1DM and Molecular mimicry” and “T1DM and epitopes” searches were conducted in PubMed, Science Direct, and Google Scholar following PRISMA guidelines. This review related original articles and case reports were collected for the compilation of all proposed proteins having a tendency of molecular mimicry. This review includes 12 original articles and 17 case reports published till date. Results: A strong association was found in peptide pairs MAP3865c/ZnT8, 4αgbp/PI, and MAP2404c/PI between MAP and human beings. Discussion: Multiple MAP proteins show strong homology to human proteins generating antibodies against pancreatic beta cells. MAP exists in dairy products, posing a high risk of transmission to human beings. An uninterrupted but silent exposure of human beings to MAP could be an environmental trigger for T1DM.

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