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.
Institute of Metabolism and Endocrinology, The Second Xiangya Hospital and the Diabetes Center, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, China.
Xia
X
Li
Departments of Pathology, Immunology, and Laboratory Medicine, and Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.
Mark A
MA
Atkinson
D000818:Animals; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D064806:Dysbiosis / Q000209:etiology / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology* / Q000503:physiopathology; D008954:Models, Biological; D010372:Pediatrics / Q000379:methods / Q000639:trends; D010539:Permeability
D015415:Biomarkers
barrier function diabetes; beta-cell autoimmunity; intestinal permeability