Comprehensive Analysis of the Physiological and Biochemical Mechanisms of Celiac Disease

Celiac disease is a chronic, immune-mediated enteropathy that occurs in genetically susceptible individuals following the ingestion of gluten, a protein complex found in wheat, barley, and rye. It is primarily characterized by an abnormal adaptive immune response, leading to inflammation and structural damage in the small intestine. The hallmark pathological feature of the disease is villous atrophy—flattening and shortening of the intestinal villi—alongside crypt hyperplasia and intraepithelial lymphocytosis, all of which contribute to impaired nutrient absorption and the clinical manifestation of malabsorption syndrome. At the molecular level, gluten is incompletely digested in the gastrointestinal tract, resulting in the accumulation of immunogenic proline- and glutamine-rich peptides. These peptides are further modified by the enzyme tissue transglutaminase (tTG) through deamidation, enhancing their affinity for HLA-DQ2 or HLA-DQ8 molecules on antigen-presenting cells in the intestinal mucosa. This interaction stimulates the activation of gluten-specific CD4+ T cells, which secrete proinflammatory cytokines and recruit other immune cells, leading to chronic inflammation and tissue injury. Additionally, patients with celiac disease develop circulating autoantibodies against tTG, which are used as diagnostic markers. While the cornerstone of treatment is a strict lifelong gluten-free diet, adherence can be challenging, and accidental exposure remains a common problem. As a result, current research is increasingly focused on developing alternative or adjunctive therapies, including enzyme supplementation, zonulin pathway blockers, and immunomodulatory agents, which aim to improve intestinal barrier function or regulate the immune response. These approaches offer promising avenues for more comprehensive disease management in the future.