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Multicenter Study
. 2022 Jun 15;14(12):2487.
doi: 10.3390/nu14122487.

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

Kamran Rostami  1   2 , Arzu Ensari  3 , Michael N Marsh  4 , Amitabh Srivastava  5 , Vincenzo Villanacci  6 , Antonio Carroccio  7 , Hamid Asadzadeh Aghdaei  8 , Julio C Bai  9 , Gabrio Bassotti  10 , Gabriel Becheanu  11 , Phoenix Bell  12 , Camillo Di Bella  13 , Anna Maria Bozzola  6 , Moris Cadei  6 , Giovanni Casella  14 , Carlo Catassi  15 , Carolina Ciacci  16 , Delia Gabriela Apostol Ciobanu  17 , Simon S Cross  18 , Mihai Danciu  17 , Prasenjit Das  19 , Rachele Del Sordo  20 , Michael Drage  21 , Luca Elli  22 , Alessio Fasano  23 , Ada Maria Florena  24 , Nicola Fusco  25 , James J Going  26 , Stefano Guandalini  27 , Catherine E Hagen  28 , David T S Hayman  29 , Sauid Ishaq  30 , Hilary Jericho  27 , Melanie Johncilla  31 , Matt Johnson  32 , Katri Kaukinen  33   34 , Adam Levene  32 , Sarah Liptrot  26 , Laura Lu  35 , Govind K Makharia  36 , Sherly Mathews  37 , Giuseppe Mazzarella  38 , Roxana Maxim  17 , Khun La Win Myint  26 , Hamid Mohaghegh-Shalmani  8 , Afshin Moradi  39 , Chris J J Mulder  40 , Ronnie Ray  32 , Chiara Ricci  41 , Mohammad Rostami-Nejad  8 , Anna Sapone  23 , David S Sanders  18 , Juha Taavela  42 , Umberto Volta  43 , Marjorie Walker  44 , Mohammad Derakhshan  26   45
Affiliations
Multicenter Study

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

Kamran Rostami et al. Nutrients. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Villus height (μm) in NCGS compared to CeD and controls, entire cohort.
Figure 2
Figure 2
Crypt depth (μm) in NCGS compared to CeD and controls, entire cohort.
Figure 3
Figure 3
Villus height to crypt depth ratio (VCR) in NCGS compared to CeD and controls, entire cohort.
Figure 4
Figure 4
Intraepithelial lymphocytes (IELs) of villi in NCGS compared to CeD and controls, entire cohort.
Figure 5
Figure 5
Architectural distortion at Marsh 0 stage. The measurable subtle changes that have been considered as a component of the spectrum of normal mucosa represent a considerable part of architectural distortion signifying the NCGS phenotype (B). This reflects in VH, VH/CrD ratio, and the IEL infiltration that were significantly different in NCGS Marsh 0 (B) compared to healthy control (A).
See this image and copyright information in PMC

References

    1. Sapone A., Bai J.C., Ciacci C., Dolinsek J., Green P.H.R., Hadjivassiliou M., Kaukinen K., Rostami K., Sanders D.S., Schumann M., et al. Spectrum of gluten-related disorders: Consensus on new nomenclature and classification. BMC Med. 2012;10:13. doi: 10.1186/1741-7015-10-13. - DOI - PMC - PubMed
    1. Villanacci V., Lanzini A., Lanzarotto F., Ricci C. Observations on the paper of Carroccio et al. “Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: Exploring a new clinical entity”. Am. J. Gastroenterol. 2013;108:619–620. doi: 10.1038/ajg.2013.22. - DOI - PubMed
    1. Carroccio A., Mansueto P., Iacono G., Soresi M., D’Alcamo A., Cavataio F. 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
    1. 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
    1. 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

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