Gluten-free diet
Gluten digestion: breakdown and development of inflammation
Gluten is present in several cereal grains and is composed of gliadins and glutenins. During digestion, peptides are formed that can elicit an immune response in individuals with celiac disease, leading to inflammation of the intestinal mucosa.
The digestion process of gluten
Gluten consists of two primary fractions, classified by their solubility: alcohol-soluble prolamins and water-insoluble glutenins. In wheat, these are referred to as gliadins and glutenins. Both fractions are complex mixtures of proteins rich in glutamine and proline, with limited amounts of essential amino acids. These glutamine- and proline-rich sequences are difficult to digest and play a key role in celiac disease. Due to genetic variability, each wheat cultivar exhibits a unique protein composition, serving as a molecular fingerprint.
Incomplete breakdown of gluten as a trigger for celiac disease
Protein digestion, including gluten, begins in the stomach with pepsin and continues in the small intestine via pancreatic and mucosal enzymes. The high glutamine and proline content in specific gluten regions impedes complete digestion, allowing peptide fragments—such as the 33-mer from α-gliadin—to persist and activate the immune system in individuals with celiac disease. This immune response involves both B and T cells, and is particularly triggered by gluten peptides that have undergone deamidation by tissue transglutaminase (tTG).
What happens after the misdirected immune response?
The immune response in the small intestine results in several pathological changes:
- Increased lymphocyte infiltration
- Mucosal damage
- Crypt hyperplasia in the small intestine
These changes alter the villus-to-crypt ratio—a hallmark of celiac disease. Severity is often assessed using the Marsh-Oberhuber classification. Research indicates that histological damage does not always correlate with symptom severity, but is more closely associated with levels of disease-specific autoantibodies such as tTG-IgA.
Sources
- Wieser H. Chemistry of gluten proteins. Food Microbiol. 2007 Apr;24(2):115-9. doi: 10.1016/j.fm.2006.07.004. Epub 2006 Sep 7. PMID: 17008153.
- Catassi C, Verdu EF, Bai JC, Lionetti E. Coeliac disease. Lancet. 2022 Jun 25;399(10344):2413-2426. doi: 10.1016/S0140-6736(22)00794-2. Epub 2022 Jun 9. PMID: 35691302.
- Török, H.P., Koletzko, S. Update on celiac disease. Internal Medicine 66, 165–173 (2025).