Abstract
Celiac disease (CD) affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS). The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD) is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten) barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS) and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA) serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ), tumor necrosis factor (TNF) and interleukin-8 (IL-8) by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading—by co-administration of additional treatments.
Highlights
Celiac disease (CD) is an autoimmune disease that affects approximately 3 million people in the United States (US) [1], only a small fraction has been diagnosed
High prevalence of CD and non-celiac gluten sensitivity (NCGS) in cereal grain-consuming societies highlights the need for novel treatments for gluten sensitivity and illustrates how many people may benefit from the successful outcome of related research
The results reported here demonstrate that the reduced gluten (RG) diet leads to a partial amelioration of gluten-induced symptoms in GS macaques
Summary
CD is an autoimmune disease that affects approximately 3 million people in the United States (US) [1], only a small fraction has been diagnosed. A non-autoimmune NCGS affects an estimated additional 6% of the population e.g., 20 million in the US [2,3]. Both CD and NCGS are characterized by sensitivity to dietary gluten. A number of novel pharmacological strategies are currently being explored for the treatment of CD These strategies include experimental drugs that reduce intestinal permeability, inhibitors of intestinal tissue transglutaminase (TG2), as well as major histocompatibility class II blockers [4]. Most of these therapies are still far from the clinic. An alternative therapy for CD and NCGS may include cereals whose storage proteins are modified to reduce the accumulation of the immunotoxic gluten epitopes [5]
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