Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic β cells. The rapid rise in T1D incidence during the past 50 y suggests environmental factors contribute to the disease. The trillion symbiotic microorganisms inhabiting the mammalian gastrointestinal tract (i.e., the microbiota) influence numerous aspects of host physiology. In this study we review the evidence linking perturbations of the gut microbiome to pancreatic autoimmunity. We discuss data from rodent models demonstrating the essential role of the gut microbiota on the development and function of the host’s mucosal and systemic immune systems. Furthermore, we review findings from human longitudinal cohort studies examining the influence of environmental and lifestyle factors on microbiota composition and pancreatic autoimmunity. Taken together, these data underscore the requirement for mechanistic studies to identify bacterial components and metabolites interacting with the innate and adaptive immune system, which would set the basis for preventative or therapeutic strategies in T1D.
This work was supported by the Canadian Institutes of Health Research (Grant 272636 to J.S.D.) and the Juvenile Diabetes Research Foundation International (Grants 17-2011-520 and 2-SRA-2015-307-Q-R to J.S.D).
Abbreviations used in this article:
- germ free
- short chain fatty acid
- specific pathogen free
- type 1 diabetes
- The Environmental Determinants of Diabetes in the Young.
- Received August 31, 2016.
- Accepted September 30, 2016.
- Copyright © 2017 by The American Association of Immunologists, Inc.