Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study

Abstract
Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS 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 VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
Description
Keywords
coeliac disease, histology, non-coeliac gluten sensitivity, normal mucosa, Biopsy, Celiac Disease, Diet, Gluten-Free, Duodenum, Glutens, Humans, Intestinal Mucosa
Citation
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. (2022). Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.. Nutrients. 14. 12. (pp. 2487-).
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