Essential amino acids in celiac disease: key roles in immunogenicity, pathogenesis, and therapeutic approaches

Celiac disease (CD) is a chronic autoimmune disorder triggered by gluten ingestion, causing intestinal damage and systemic complications. Essential amino acids (EAAs) play crucial roles in immune function, intestinal integrity, and metabolic regulation; however, their malabsorption in CD contributes to disease progression. Tryptophan dysregulation may influence mood disorders in CD, while phenylalanine and lysine are linked to immune activation and gluten modification. Methionine impacts antioxidant defense and homocysteine metabolism, and disruptions in both pathways have been observed in CD patients. Branched-chain amino acids (BCAAs), crucial for muscle synthesis, remain deficient even in treated patients, suggesting long-term metabolic effects. Threonine, vital for gut barrier function, has been reported to show increased levels in CD, potentially reflecting altered metabolism and disease progression. Arginine metabolism shifts toward pro-inflammatory nitric oxide production, exacerbating intestinal damage. EAA imbalances may serve as biomarkers for disease activity, severity, and treatment response. Altered plasma and fecal amino acid profiles correlate with disease progression, offering diagnostic and monitoring potential. Addressing EAA deficiencies through targeted supplementation or dietary interventions could enhance intestinal healing, mitigate complications, and improve outcomes beyond a gluten-free diet (GFD). This review examines the interplay between EAAs and CD pathogenesis, highlighting their roles in immune modulation, gut barrier maintenance, systemic metabolic effects, and potential as disease biomarkers.