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

Rostami, K.; Ensari, A.; Marsh, M.N.; Srivastava, A; Villanacci, V; Carroccio, A; Asadzadeh Aghdaei, H; Bai, J.C; Bassotti, G; Becheanu, G; Bell, P; Di Bella, C; Bozzola, A.M; Cadei, M; Casella, G; Catassi , C; Ciacci, C; Apostel Ciobanu, D.G; Cross, S.S; Danciu, M; Das, P; Del Sordo , R; Drage, M; Elli, L; Fasano, A; Florena, A.M; Fusco, N; Going , J.J; Guandalini, S; Hagen, C.E; Hayman, D.T.S; Ishaq, S; Jericho, H; Johncilla, M; Johnson, M; Kaukinen, K; Levene, A; Liptrot, S; Lu, L; Makharia, G.K; Mathews, S; Mazzarella, G; Maxim , R; Myint , K.L.W; Mohaghegh-Shalmani, H; Moradi, A; Mulder, C..J.J; Ray, R; Ricci, C; Rostami-Nejad, M; Sapone, A; Sanders, D.S; 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

Authors

Rostami, K.

Ensari, A.

Marsh, M.N.

Srivastava, A

Villanacci, V

Carroccio, A

Asadzadeh Aghdaei, H

Bai, J.C

Bassotti, G

Becheanu, G

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Issue Date

2022

Type

Published Abstract

Keywords

Research Subject Categories::MEDICINE::Dermatology and venerology,clinical genetics, internal medicine::Internal medicine::Gastroenterology

Abstract

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. Keywords: coeliac disease; histology; non-coeliac gluten sensitivity; normal mucosa. PubMed Disclaimer Conflict of interest statement The authors declare no conflict of interest. Figures Figure 1 Figure 1 Villus height (μm) in NCGS… Figure 2 Figure 2 Crypt depth (μm) in NCGS… Figure 3 Figure 3 Villus height to crypt depth… Figure 4 Figure 4 Intraepithelial lymphocytes (IELs) of villi… Figure 5 Figure 5 Architectural distortion at Marsh 0… Similar articles Histopathology of non-coeliac gluten sensitivity. Kirmizi A, Salman FG, Savas B, Kalkan C, Soykan I, Ensari A. Virchows Arch. 2022 Feb;480(2):315-322. doi: 10.1007/s00428-021-03257-5. Epub 2022 Jan 11. PMID: 35018514 Histological, immunohistochemical and mRNA gene expression responses in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded duodenal biopsies. Taavela J, Viiri K, Popp A, Oittinen M, Dotsenko V, Peräaho M, Staff S, Sarin J, Leon F, Mäki M, Isola J. BMC Gastroenterol. 2019 Nov 15;19(1):189. doi: 10.1186/s12876-019-1089-7. PMID: 31730447 Free PMC article. 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Non Celiac Wheat Sensitivity diagnosed by double-blind placebo controlled challenge exploring a new entity. Am. J. Gastroenterol. 2012;107:1898–1906. doi: 10.1038/ajg.2012.236. - DOI - PubMed Rostami K., Aldulaimi D., Holmes G., Johnson M.W., Robert M., Srivastava A., Fléjou J.-F., Sanders D.S., Volta U., Derakhshan M.H., et al. Microscopic enteritis: Bucharest consensus. World J. Gastroenterol. 2015;21:2593–2604. doi: 10.3748/wjg.v21.i9.2593. - DOI - PMC - PubMed Uhde M., Ajamian M., Caio G., De Giorgio R., Indart A., Green P.H., Verna E.C., Volta U., Alaedini A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016;65:1930–1937. doi: 10.1136/gutjnl-2016-311964. - DOI - PMC - PubMed

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. Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study. Nutrients. 2022 Jun 15;14(12):2487. doi: 10.3390/nu14122487. PMID: 35745217; PMCID: PMC9230100.