Wheat, especially due to its gluten content, is well-known as a major food antigen worldwide. As such, it has been implicated as a factor in several disorders, including celiac disease (CeD), dermatitis Herpetiformis, wheat allergy (WA), gluten-induced ataxia and, more recently, in non-celiac wheat sensitivity (NCWS).
Sensitivity to gluten/wheat manifests in specific symptoms, both intestinal and extraintestinal, that can be similar to the clinical picture of CeD. Extraintestinal NCWS symptoms may be neuropsychiatric symptoms, potentially related to microbial translocation and systemic immune activation [1]. After ruling out CeD and WA, diagnosis of NCWS is made by verifying a positive response to a gluten-free diet.
Biomarkers as clues
NCWS is immune-mediated, however the immune response is distinct from CeD and WA. The immune response is associated with antibody production to wheat gluten, specifically IgG2, IgG4 and IgM, and systemic innate immune activation to lipopolysaccharides (LPS) [2]. Serologic evidence of NCWS includes intestinal cell damage and elevated intestinal fatty acid-binding protein (FABP2) [1].
Still, more research is needed to understand the connection between intestinal inflammation, immune activation, epithelial barrier dysfunction and potential microbial translocation in NCWS. Such findings could support identification of diagnostic biomarkers and serve as potential targets for NCWS treatment, as well as other conditions related to intestinal permeability, like irritable bowel syndrome (IBS).
New research on non-celiac wheat sensitivity
The objective of a recent study was to evaluate the structural and inflammatory features of NCWS compared to controls and CeD with milder enteropathy (Marsh I-II), since the histological changes induced by gluten in the duodenal mucosa of patients with NCWS is not well defined.
Methods
The researchers examined samples from 9 countries:
- 262 biopsies of control cases with normal gastroscopy and histological findings
- 261 biopsies of cases with CeD
- 175 biopsies of cases with NCWS
From these samples, villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serological, and demographic parameters were quantified.
Results
- The median VH in NCWS was significantly shorter (600, IQR: 400–705) than controls (900, IQR: 667–1112) (p < 0.001).
- NCWS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390–620) vs. 427 µm (IQR: 348–569, p = 0·176)].
- The proportion of VCR in the NCWS with a Marsh 0 was lower than in the control group (p < 0.001).
- The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001).
- IEL densities in Marsh I-II NCWS and CeD groups were similar.
In conclusion, the duodenal mucosa in the NCWS exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture. These findings support the larger body of research that provides greater insight into the mechanism behind NCWS and potential treatment paths.
References
- Volta U, De Giorgio R, Caio G, Uhde M, Manfredini R, Alaedini A. Nonceliac Wheat Sensitivity: An Immune-Mediated Condition with Systemic Manifestations. Gastroenterol Clin North Am. 2019;48(1):165-182. doi:10.1016/j.gtc.2018.09.012
- Uhde M, Caio G, De Giorgio R, Green PH, Volta U, Alaedini A. Subclass Profile of IgG Antibody Response to Gluten Differentiates Nonceliac Gluten Sensitivity From Celiac Disease. Gastroenterology. 2020;159(5):1965-1967.e2. doi:10.1053/j.gastro.2020.07.032
- Rostami K, Ensari A, Marsh MN, Srivastava A, Villanacci V, Carroccio A, Asadzadeh Aghdaei H, Bai JC, Bassotti G, Becheanu G, Bell P, Di Bella C, Bozzola AM, Cadei M, Casella G, Catassi C, Ciacci C, Apostol Ciobanu DG, Cross SS, Danciu M, Das P, Del Sordo R, Drage M, Elli L, Fasano A, Florena AM, Fusco N, Going JJ, Guandalini S, Hagen CE, Hayman DTS, Ishaq S, Jericho H, Johncilla M, Johnson M, Kaukinen K, Levene A, Liptrot S, Lu L, Makharia GK, Mathews S, Mazzarella G, Maxim R, La Win Myint K, Mohaghegh-Shalmani H, Moradi A, Mulder CJJ, Ray R, Ricci C, Rostami-Nejad M, Sapone A, Sanders DS, Taavela J, Volta U, Walker M, Derakhshan M. Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study. Nutrients. 2022; 14(12):2487. https://doi.org/10.3390/nu14122487
