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

Kamran Rostami; Arzu Ensari; Michael N. Marsh; Amitabh Srivastava; Vincenzo Villanacci; Antonio Carroccio; Hamid Asadzadeh Aghdaei; Julio C. Bai; Gabrio Bassotti; Gabriel Becheanu; Phoenix Bell; Camillo Di Bella; Anna Maria Bozzola; Moris Cadei; Giovanni Casella; Carlo Catassi; Carolina Ciacci; Delia Gabriela Apostol Ciobanu; Simon S. Cross; Mihai Danciu; Prasenjit Das; Rachele Del Sordo; Michael Drage; Luca Elli; Alessio Fasano; Ada Maria Florena; Nicola Fusco; James J. Going; Stefano Guandalini; Catherine E. Hagen; David T.S. Hayman; Sauid Ishaq; Hilary Jericho; Melanie Johncilla; Matt Johnson; Katri Kaukinen; Adam Levene; Sarah Liptrot; Laura Lu; Govind K. Makharia; Sherly Mathews; Giuseppe Mazzarella; Roxana Maxim; Khun La Win Myint; Hamid Mohaghegh-Shalmani; Afshin Moradi; Chris J.J. Mulder; Ronnie Ray; Chiara Ricci; Mohammad Rostami-Nejad; Anna Sapone; David S. Sanders; Juha Taavela; Umberto Volta; Marjorie Walker; Mohammad Derakhshan

doi:10.3390/nu14122487

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

Kamran Rostami, Arzu Ensari, Michael N. Marsh, Amitabh Srivastava, Vincenzo Villanacci, Antonio Carroccio, Hamid Asadzadeh Aghdaei, Julio C. Bai, Gabrio Bassotti, Gabriel Becheanu, Phoenix Bell, Camillo Di Bella, Anna Maria Bozzola, Moris Cadei, Giovanni Casella, Carlo Catassi, Carolina Ciacci, Delia Gabriela Apostol Ciobanu, Simon S. Cross, Mihai DanciuPrasenjit Das, Rachele Del Sordo, Michael Drage, Luca Elli, Alessio Fasano, Ada Maria Florena, Nicola Fusco, James J. Going, Stefano Guandalini, Catherine E. Hagen, David T.S. Hayman, Sauid Ishaq, Hilary Jericho, Melanie Johncilla, Matt Johnson, Katri Kaukinen, Adam Levene, Sarah Liptrot, Laura Lu, Govind K. Makharia, Sherly Mathews, Giuseppe Mazzarella, Roxana Maxim, Khun La Win Myint, Hamid Mohaghegh-Shalmani, Afshin Moradi, Chris J.J. Mulder, Ronnie Ray, Chiara Ricci, Mohammad Rostami-Nejad, Anna Sapone, David S. Sanders, Juha Taavela, Umberto Volta, Marjorie Walker, Mohammad Derakhshan

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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.

Original language	English
Article number	2487
Number of pages	14
Journal	NUTRIENTS
Volume	14
Issue number	12
DOIs	https://doi.org/10.3390/nu14122487
Publication status	Published - Jun 2022
Publication type	A1 Journal article-refereed

Funding

We are grateful for the technical assistance of Clare Orange, Jennifer Hay, and Hannah Morgan who tirelessly contributed to Derakhshan’s team in the Digital Histology Section at Queen Elizabeth University Hospital, Glasgow, UK. Many thanks to David Rowlands, histopatholo-gist at the Royal Wolverhampton NHS Trust, New Cross Hospital for his dedication in guiding Laura Lu in morphometric assessment. We also would like to thank Jafar Ali, gastroenterologist at Milton Keynes University Hospital, UK for his contribution to data collection.

Keywords

coeliac disease
histology
non-coeliac gluten sensitivity
normal mucosa

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Food Science
Nutrition and Dietetics

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10.3390/nu14122487Licence: CC BY

nutrients-14-02487-v3Final published version, 2.43 MBLicence: CC BY

https://urn.fi/URN:NBN:fi:tuni-202208206578Licence: CC BY

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Rostami, K., Ensari, A., Marsh, M. N., Srivastava, A., Villanacci, V., Carroccio, A., Aghdaei, H. A., Bai, J. C., Bassotti, G., Becheanu, G., Bell, P., Bella, C. D., Bozzola, A. M., Cadei, M., Casella, G., Catassi, C., Ciacci, C., Ciobanu, D. G. A., Cross, S. S., ... Derakhshan, M. (2022). Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study. NUTRIENTS, 14(12), Article 2487. https://doi.org/10.3390/nu14122487

@article{170a2ab589e347b5a9ab1fb56d8a8b33,

title = "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.",

keywords = "coeliac disease, histology, non-coeliac gluten sensitivity, normal mucosa",

author = "Kamran Rostami and Arzu Ensari and Marsh, {Michael N.} and Amitabh Srivastava and Vincenzo Villanacci and Antonio Carroccio and Aghdaei, {Hamid Asadzadeh} and Bai, {Julio C.} and Gabrio Bassotti and Gabriel Becheanu and Phoenix Bell and Bella, {Camillo Di} and Bozzola, {Anna Maria} and Moris Cadei and Giovanni Casella and Carlo Catassi and Carolina Ciacci and Ciobanu, {Delia Gabriela Apostol} and Cross, {Simon S.} and Mihai Danciu and Prasenjit Das and Sordo, {Rachele Del} and Michael Drage and Luca Elli and Alessio Fasano and Florena, {Ada Maria} and Nicola Fusco and Going, {James J.} and Stefano Guandalini and Hagen, {Catherine E.} and Hayman, {David T.S.} and Sauid Ishaq and Hilary Jericho and Melanie Johncilla and Matt Johnson and Katri Kaukinen and Adam Levene and Sarah Liptrot and Laura Lu and Makharia, {Govind K.} and Sherly Mathews and Giuseppe Mazzarella and Roxana Maxim and Myint, {Khun La Win} and Hamid Mohaghegh-Shalmani and Afshin Moradi and Mulder, {Chris J.J.} and Ronnie Ray and Chiara Ricci and Mohammad Rostami-Nejad and Anna Sapone and Sanders, {David S.} and Juha Taavela and Umberto Volta and Marjorie Walker and Mohammad Derakhshan",

note = "Funding Information: We are grateful for the technical assistance of Clare Orange, Jennifer Hay, and Hannah Morgan who tirelessly contributed to Derakhshan{\textquoteright}s team in the Digital Histology Section at Queen Elizabeth University Hospital, Glasgow, UK. Many thanks to David Rowlands, histopatholo-gist at the Royal Wolverhampton NHS Trust, New Cross Hospital for his dedication in guiding Laura Lu in morphometric assessment. We also would like to thank Jafar Ali, gastroenterologist at Milton Keynes University Hospital, UK for his contribution to data collection. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jun,

doi = "10.3390/nu14122487",

language = "English",

volume = "14",

journal = "NUTRIENTS",

issn = "2072-6643",

publisher = "MDPI",

number = "12",

}

Rostami, K, Ensari, A, Marsh, MN, Srivastava, A, Villanacci, V, Carroccio, A, Aghdaei, HA, Bai, JC, Bassotti, G, Becheanu, G, Bell, P, Bella, CD, Bozzola, AM, Cadei, M, Casella, G, Catassi, C, Ciacci, C, Ciobanu, DGA, Cross, SS, Danciu, M, Das, P, Sordo, RD, 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, Myint, KLW, 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, vol. 14, no. 12, 2487. https://doi.org/10.3390/nu14122487

TY - JOUR

T1 - Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity

T2 - A Multicentre Study

AU - Rostami, Kamran

AU - Ensari, Arzu

AU - Marsh, Michael N.

AU - Srivastava, Amitabh

AU - Villanacci, Vincenzo

AU - Carroccio, Antonio

AU - Aghdaei, Hamid Asadzadeh

AU - Bai, Julio C.

AU - Bassotti, Gabrio

AU - Becheanu, Gabriel

AU - Bell, Phoenix

AU - Bella, Camillo Di

AU - Bozzola, Anna Maria

AU - Cadei, Moris

AU - Casella, Giovanni

AU - Catassi, Carlo

AU - Ciacci, Carolina

AU - Ciobanu, Delia Gabriela Apostol

AU - Cross, Simon S.

AU - Danciu, Mihai

AU - Das, Prasenjit

AU - Sordo, Rachele Del

AU - Drage, Michael

AU - Elli, Luca

AU - Fasano, Alessio

AU - Florena, Ada Maria

AU - Fusco, Nicola

AU - Going, James J.

AU - Guandalini, Stefano

AU - Hagen, Catherine E.

AU - Hayman, David T.S.

AU - Ishaq, Sauid

AU - Jericho, Hilary

AU - Johncilla, Melanie

AU - Johnson, Matt

AU - Kaukinen, Katri

AU - Levene, Adam

AU - Liptrot, Sarah

AU - Lu, Laura

AU - Makharia, Govind K.

AU - Mathews, Sherly

AU - Mazzarella, Giuseppe

AU - Maxim, Roxana

AU - Myint, Khun La Win

AU - Mohaghegh-Shalmani, Hamid

AU - Moradi, Afshin

AU - Mulder, Chris J.J.

AU - Ray, Ronnie

AU - Ricci, Chiara

AU - Rostami-Nejad, Mohammad

AU - Sapone, Anna

AU - Sanders, David S.

AU - Taavela, Juha

AU - Volta, Umberto

AU - Walker, Marjorie

AU - Derakhshan, Mohammad

N1 - Funding Information: We are grateful for the technical assistance of Clare Orange, Jennifer Hay, and Hannah Morgan who tirelessly contributed to Derakhshan’s team in the Digital Histology Section at Queen Elizabeth University Hospital, Glasgow, UK. Many thanks to David Rowlands, histopatholo-gist at the Royal Wolverhampton NHS Trust, New Cross Hospital for his dedication in guiding Laura Lu in morphometric assessment. We also would like to thank Jafar Ali, gastroenterologist at Milton Keynes University Hospital, UK for his contribution to data collection. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

KW - coeliac disease

KW - histology

KW - non-coeliac gluten sensitivity

KW - normal mucosa

U2 - 10.3390/nu14122487

DO - 10.3390/nu14122487

M3 - Article

C2 - 35745217

AN - SCOPUS:85131910570

SN - 2072-6643

VL - 14

JO - NUTRIENTS

JF - NUTRIENTS

IS - 12

M1 - 2487

ER -

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

Abstract

Funding

Keywords

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