Role of the gastrointestinal ecosystem in the development of type 1 diabetes

Abstract

A new emphasis has been put on the role of the gastrointestinal (GI) ecosystem in autoimmune diseases; however, there is limited knowledge about its role in type 1 diabetes (T1D). Distinct differences have been observed in intestinal permeability, epithelial barrier function, commensal microbiota, and mucosal innate and adaptive immunity of patients and animals with T1D, when compared with healthy controls. The non-obese diabetic (NOD) mouse and the BioBreeding diabetes prone (BBdp) rat are the most commonly used models to study T1D pathogenesis. With the increasing awareness of the importance of the GI ecosystem in systemic disease, it is critical to understand the basics, as well as the similarities and differences between rat and mouse models and human patients. This review examines the current knowledge of the role of the GI ecosystem in T1D and indicates the extensive opportunities for further investigation that could lead to biomarkers and therapeutic interventions for disease prevention and/or modulation.

Keywords: animal models; epithelium; intestine; microbiota; type I diabetes.

Figure 1

Intestinal homeostasis is maintained by a healthy microbial population, mucin layer, antimicrobial peptides, and tight junction proteins. Together these factors prevent or limit the exposure of bacteria and luminal antigens to the epithelium, which result in non-activated or tolerant immune system. In a diseased state when alterations are made to the microbial population, mucin layer, antimicrobial peptides, and tight junction proteins, bacteria and luminal antigens are able cross the epithelial layer. Once bacteria and other luminal antigens have crossed the epithelial layer the immune system is activated, leading to diseases, such as type 1 diabetes.