Influence of Host Immunoregulatory Genes, ER Stress and Gut Microbiota on the Shared Pathogenesis of Inflammatory Bowel Disease and Type 1 Diabetes

Abstract

Inflammatory bowel disease (IBD) with its two distinct entities, Crohn‘s disease and ulcerative colitis, and Type 1 diabetes mellitus (T1D) are autoimmune diseases. The prevalence of these diseases continues to rapidly rise in the industrialized world. Despite the identification of several genetic loci that are associated with both IBD and T1D, thus far, there is a paucity of epidemiological data to support a clinical overlap. In an effort to better understand the underlying pathogenic mechanisms of both IBD and T1D, this review summarizes the literature about these related autoimmune diseases, describes the most recent advances in their etiopathogenesis and emphasizes the genetic and nongenetic factors that exercise a differential influence. Genome-wide association studies have identified genetic loci with a role in immune response regulation that are linked to both IBD (particularly Crohn‘s disease) and T1D. Some of these genetic loci (e.g., IL-18RAP) have a divergent role, conferring risk for one disease and protection for the other. Recent evidence highlights an important role of gut microbiota and cellular responses (e.g., endoplasmic reticulum stress) in the pathogenesis of both IBD and T1D.

KEYWORDS::

• autoimmune diseases
• Crohn‘s disease
• host genetics
• IL-18RAP
• SNP
• Type 1 diabetes mellitus

Acknowledgments

The authors wish to thank M Mohamadzadeh, J Owen and B Sahay for the critical review of the manuscript.

Financial & competing interests disclosure

This study was supported by a NIH grant (RO1 CA113975-A2) and a Gatorade fund to SC Glover, and a JDRF Career Development Award (2-2012-280) and an American Diabetes Association grant (7–13-BS-022) to TM Brusko. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported by a NIH National Institutes of Health grant (RO1 CA113975-A2) and a Gatorade fund to SC Glover, and a JDRF Career Development Award (2-2012-280) and an American Diabetes Association grant (7–13-BS-022) to TM Brusko. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.