The role for gut permeability in the pathogenesis of type 1 diabetes - a solid or leaky concept?

Increasing evidence, both functional and morphological, supports the concept of increased intestinal permeability as an intrinsic characteristic of type 1 diabetes (T1D) in both humans and animal models of the disease. Often referred to as a leaky gut', its mechanistic impact on the pathogenesis of T1D remains unclear. Hypotheses that this defect influences immune responses against antigens (both self and non-self) predominate, yet others argue hyperglycemia and insulitis may contribute to increased gut permeability in T1D. To address these complicated issues, we herein review the many conceptual role(s) for a leaky gut in the pathogenesis of T1D and suggest ways that if true, therapeutic interventions aimed at the gut-pancreas axis may prove promising for future therapeutic interventions.