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

Pediatr Diabetes. 2015 Nov;16(7):485-92. doi: 10.1111/pedi.12305. Epub 2015 Aug 13.


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.

Keywords: barrier function diabetes; beta-cell autoimmunity; intestinal permeability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / microbiology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Dysbiosis / etiology
  • Dysbiosis / immunology
  • Dysbiosis / microbiology
  • Dysbiosis / physiopathology
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / microbiology
  • Gastrointestinal Tract / physiopathology*
  • Humans
  • Infant
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / physiopathology
  • Models, Biological*
  • Pediatrics / methods
  • Pediatrics / trends
  • Permeability


  • Biomarkers