Diet, Gut, and Type 1 Diabetes: Role of Wheat-Derived Peptides?

Abstract

The role of the gut and gut-associated lymphoid tissue in the development of type 1 diabetes has come into the research focus over the last 20 years. Accumulated evidence suggests that the gut is involved in the pathogenesis of this immune-mediated disease, and there seem to be several mechanisms by which such an effect may be mediated (1). Decreased microbial diversity in the gut, increased intestinal permeability, local inflammation in the gastrointestinal tract, and abnormal mucosal immune responses all may contribute to the appearance of β-cell autoimmunity and further progression to overt type 1 diabetes. The intestinal mucosa comprises the largest surface area in the body, and the gut-associated lymphoid tissue represents the most extensive immune organ. The gut plays accordingly a crucial role in the interaction between the host and the environment. Given that type 1 diabetes is the unfortunate consequence of the combined effects of the individual genetic setup and exogenous and host-related factors, it is not surprising that the gut might be involved in the process leading to clinical disease. In this issue of Diabetes , Mojibian et al. (2) report that approximately half of the patients with type 1 diabetes, whom they studied, had a proliferative T-cell response to dietary wheat polypeptides and that the cytokine profile of the response was predominantly proinflammatory. A positive T-cell response to wheat polypeptides was associated with the HLA DR4-DQ8 haplotype but surprisingly not with the HLA DR3-DQ2 haplotype, which confers strong susceptibility to celiac disease. The investigators interpret their observations as reflecting a diabetes-related inflammatory state in the gut immune system associated with defective oral tolerance and a possible gut …