Gluten Tolerance through Microbial and Cultural Adaptation: A Holistic Model for Celiac Disease and Non-celiac Gluten Sensitivity

Aim and background: Celiac disease (CD) and nonceliac gluten sensitivity (NCGS) are increasing in public and scientific focus. Interestingly, regions with traditionally high gluten consumption such as Turkey, Iran, and the Mediterranean show lower CD prevalence than the Western countries. This paradox indicates that genetic predisposition alone, such as HLA DQ2 or DQ8 carriage, does not fully explain gluten intolerance. Understanding environmental, microbial, and cultural contributors may clarify the development of gluten tolerance. Methods: This narrative review synthesizes current evidence from epidemiology, microbiology, immunology, and nutritional science to propose an integrative hypothesis. Relevant literature was examined to explore interactions among diet, gut microbiota, and immune tolerance mechanisms that influence responses to gluten exposure. Results: can enzymatically degrade immunogenic gluten peptides including the 33-mer α2-gliadin fragments. Reduced microbial diversity and the consumption of ultra-processed foods may contribute to heightened gluten sensitivity and immune dysregulation. Conclusion: Gluten is not inherently toxic; its immunogenicity depends on host microbiota composition, environmental exposures, and dietary context. A systems biology approach that integrates microbial ecology, evolutionary adaptation, and immunonutrition may better explain gluten tolerance variability across populations. Clinical significance: Recognizing gluten tolerance as a modifiable, microbiota influenced process may guide more individualized dietary recommendations, reduce unnecessary gluten avoidance, and promote evidence-based clinical management of gluten-related disorders. How to cite this article: Bektaş A, Ulusoy M. Gluten Tolerance through Microbial and Cultural Adaptation: A Holistic Model for Celiac Disease and Non-celiac Gluten Sensitivity. Euroasian J Hepato-Gastroenterol 2025;15(2):185-189.