Cocoa Attenuates Gluten-induced Pathogenesis in a Preclinical Model of Celiac Disease

Celiac disease (CeD) is an autoimmune-mediated disorder triggered by gluten ingestion. Strict adherence to a gluten-free diet (GFD) is currently the only available treatment, yet it presents nutritional and lifestyle challenges. Polyphenols and other bioactive food compounds have shown potential in modulating inflammation and gut health. This study evaluated the impact of cocoa, a polyphenol-rich food, on CeD pathogenesis in a preclinical model. DQ8-D^d-villin-IL-15tg mice with predisposition to CeD were fed either a GFD (REF), a gluten-containing diet (GLI), or a gluten-containing diet supplemented with cocoa (GLI+COCOA) for 25 days. Outcomes assessed included intestinal histology, antibody (Ab) levels, cytokine and immunoglobulin profiles and mesenteric lymph node lymphocytes' phenotypes. Cocoa administration limited gluten-induced intestinal villous atrophy and reduced anti-gliadin Abs, while significantly decreasing the secretion of pro-inflammatory cytokines. Moreover, cocoa normalized the Ig isotype profile dysregulated by gluten intake. Cocoa intake exerts a protective effect against key hallmarks of CeD, attenuating inflammation and limiting the damage to the intestinal structure. These findings support cocoa as a promising complementary dietary strategy to modulate CeD-related manifestations, although additional translational studies are warranted.