Non-celiac gluten/wheat sensitivity (NCGS)
What is gluten/wheat sensitivity?
Non-celiac gluten sensitivity, also known as gluten/wheat sensitivity, is a syndrome that manifests itself through gastrointestinal and extraintestinal discomfort that appears after consuming foods containing gluten in people who have been medically diagnosed as not having celiac disease or wheat allergy.
Gluten sensitivity without being celiac: a new perspective on the term
In addition to gluten, other components of wheat-such as amylase-trypsin inhibitors (ATIs) and FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols)-can cause similar symptoms. For this reason, the term 'non-celiac wheat sensitivity' (NCWS) is increasingly used in scientific literature, as it is considered more accurate than 'non-celiac gluten sensitivity' (NCGS), since it better reflects the diversity of possible triggers.
Differences from celiac disease and wheat allergy
The three cereal-related diseases (gluten/wheat sensitivity, celiac disease, and wheat allergy) have similar symptoms and can therefore be easily confused when it comes to diagnosis. It is therefore important to understand their pathogenesis and reaction mechanisms:
- Celiac disease (CD) is an autoimmune disorder in which gluten intake triggers chronic inflammation of the small intestine mucosa. It is characterized by the presence of specific autoantibodies, such as antitransglutaminase, and by histological alterations that can be classified according to the Marsh scale.
- Wheat allergy (WA) is an IgE-mediated immune reaction to specific wheat proteins. Symptoms usually appear quickly after ingestion and can range from mild skin reactions to anaphylaxis.
- Non-celiac gluten/wheat sensitivity (NCGS) is a diagnosis of exclusion that is established once celiac disease and wheat allergy have been ruled out. Affected individuals experience symptoms similar to those of celiac disease after consuming foods containing gluten or wheat, but without the presence of specific autoantibodies, without associated autoimmune comorbidities, and, in most cases, without significant alterations in the intestinal mucosa (Marsh 0-1).
Differences between celiac disease, gluten/wheat sensitivity, and wheat allergy
| Characteristic | Celiac disease | Wheat allergy (IgE-mediated) | Wheat allergy (non-IgE-mediated) | Gluten/wheat sensitivity |
|---|---|---|---|---|
| Route of exposure | Oral | Inhalation or oral | Oral | Oral |
| Onset of symptoms after exposure | Hours to months | Immediately | Days to weeks | Hours to days |
| Distribution by sex | 60-70% women | No difference | No difference | Predominance of women |
| Extraintestinal manifestations | Liver, joints/bones, skin, blood, CNS | Respiratory tract, skin, circulation (anaphylaxis) | None | Skin, joints/muscles, CNS |
| HLA predisposition | HLA-DQ2/DQ8 | None | None | HLA-DQ2/DQ8 overrepresented |
| Prognosis | Chronic disease | Tolerance in 2/3 of children up to age 12 | Unclear | Unclear |
| Treatment | Strict, lifelong gluten-free diet. Even trace amounts of gluten can cause inflammation and long-term complications. | Elimination of the allergen (avoid wheat in all forms). In severe cases: emergency medication (e.g., epinephrine auto-injector). | Wheat-free diet, if necessary, anti-inflammatory therapy (e.g., corticosteroids). | Low-gluten or gluten-free diet, individually tailored. Complete elimination is not always necessary. |
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Read moreSources
- Størdal K, Kurppa K. Celiac disease, non-celiac wheat sensitivity, wheat allergy: clinical and diagnostic aspects. Semin Immunol. March 2025; 77:101930. doi: 10.1016/j.smim.2025.101930. Epub January 9, 2025. PMID: 39793259.
- Catassi C, Elli L, Bonaz B, Bouma G, Carroccio A, Castillejo G, Cellier C, Cristofori F, de Magistris L, Dolinsek J, Dieterich W, Francavilla R, Hadjivassiliou M, Holtmeier W, Körner U, Leffler DA, Lundin KE, Mazzarella G, Mulder CJ, Pellegrini N, Rostami K, Sanders D, Skodje GI, Schuppan D, Ullrich R, Volta U, Williams M, Zevallos VF, Zopf Y, Fasano A. Diagnosis of non-celiac gluten sensitivity (NCGS): Salerno expert criteria. Nutrients. 2015 Jun 18;7(6):4966-77. doi: 10.3390/nu7064966. PMID: 26096570; PMCID: PMC4488826.