The Economic Burden of Gluten-Free Products and the Potential of Dietary Inhibitors of Transglutaminase-2

Celiac disease (CD) is a chronic immune-mediated disease of the small intestine caused by the ingestion of gluten. Gluten presents to the intestine largely intact where it is deamidated by Transglutaminase-2 (TG2), increasing affinity for Human Leukocyte Antigen DQ2 (HLA-DQ2) and forming a complex that elicits an inflammatory response ultimately leading to villous atrophy. The only current treatment is strict adherence to a gluten-free diet, though TG2 inhibition is an attractive therapy due its central role in CD pathogenesis. Cocoa contains procyanidin-B2, theobromine and caffeine and may be capable of inhibiting TG2-induced intestinal inflammation and reduce CD symptoms. Procyanidin-B2 rich cocoa extracts reduced TG2 levels by up to 77% in vitro using Caco-2 cells. Significant TG2 inhibition was seen when cocoa extracts contained at least 8.5 μM procyanidin-B2 (p\u3c0.05). Other CD inflammatory biomarkers including COX-2 and IL-15 were also significantly decreased in the presence of cocoa extracts. Serum cytokines IL-6, IL-8 and IL-1β are commonly used to monitor CD and were analyzed using ELISA to confirm the inhibition of inflammatory biomarkers. This study shows promising results for use of a bioactive-rich cocoa product as a dietary inhibitor of TG2 that can be used with wheat-based products as an alternative therapy in CD