Immunomodulation with microbial vaccines to prevent type 1 diabetes mellitus

Abstract

Selected bacteria, viruses, parasites and nonliving, immunologically active microbial substances prevent autoimmune diabetes in animal models. Such agents might also have a protective effect in humans by providing immune stimuli critical during childhood development. The 'hygiene hypothesis' proposes that reduced exposure to environmental stimuli, including microbes, underlies the rising incidence of childhood autoimmune diseases, including type 1 diabetes mellitus (T1DM). This hypothesis is supported by data that highlight the importance of infant exposure to environmental microbes for appropriate development of the immune system, which might explain the observation that administration of microbes or their components inhibits autoimmune disease in animals. This finding raises the possibility of using live, nonpathogenic microbes (for example, probiotics) or microbial components to modulate or 're-educate' the immune system and thereby vaccinate against T1DM. Progress has been assisted by the identification of receptors and pathways through which gut microbes influence development of the immune system. Such mechanistic data have moved a field that was once regarded as being on the scientific fringe to the mainstream, and support increased funding to advance this promising area of research in the hope that it might deliver the long awaited answer of how to safely prevent T1DM.

Oral Administration of Recombinant Lactococcus lactis Expressing HSP65 and Tandemly Repeated P277 Reduces the Incidence of Type I Diabetes in Non-Obese Diabetic Mice

“…Different therapeutic approaches have been exploited aimed at regulating this autoimmune response, including broad immunosuppressive drugs, antibody-based immunotherapies and antigen-based immunotherapy [1], [2]. However, the substantial short- and long-term toxic effects of immunosuppressive agents have blocked the adoption of nonspecific immunosuppression into clinical practice [3]. Antibody-based immunotherapies failed to discriminate between autoreactive versus non-autoimmune effectors.…”

RETRACTED: Preventative and Therapeutic Role of Probiotics in Various Allergic and Autoimmune Disorders: An Up-to-Date Literature Review of Essential Experimental and Clinical Data

“…The incidence of spontaneous type 1 diabetes is directly correlated with the sanitary conditions of the animal facilities, for both the nonobese diabetes mouse and the bio-breeding diabetes-prone rat: the lower the infectious burden, the higher the disease incidence. [15][16][17][18][19]25 Diabetes has a very low incidence and may even be absent in nonobese diabetes mice bred in ''conventional'' facilities, whereas the incidence is close to 100% in female mice bred in specific pathogen-free conditions. 35 Furthermore, bio-breeding diabetes-prone rats subject to cesarean derivation have been noted to develop accelerated disease due to lack of contamination with microbiota in birth canal.…”

“…17 Immunization with microbial agents at an early age may offer an important new direction for the immunotherapy of type 1 diabetes. 17,18 The protective effect of a probiotic and a bacterial extract was reported on the onset of diabetes in nonobese diabetic mice. 19 These findings raise the possibility of using live, nonpathogenic microbes (eg, probiotics) or microbial components to modulate or ''reeducate'' the immune system.…”

Echovirus Epidemics, Autoimmunity, and Type 1 Diabetes

“…Taken together, these data suggest that not only the adaptive immune response provides protection against exposure to diabetogenic viruses, but also the innate immune system. Multiple non-specific stimuli acting on the immune system during early childhood and before puberty are hoped to provide an effective strategy to reduce the increasing incidence of T1D (Petrovsky, 2010).…”