Dataset Information

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.

SUBMITTER: Rostami K

PROVIDER: S-EPMC9230100 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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

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

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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 ( ...[more]

PMID: 35745217

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Project description:Non-coeliac gluten sensitivity (NCGS) refers to patients with primarily gastrointestinal symptoms without enteropathy that symptomatically benefit from gluten-free diet (GFD). Little is known about its pathophysiology, propensity to neurological manifestations, and if these differ from patients with coeliac disease (CD). We investigated the clinical and immunological characteristics of patients presenting with neurological manifestations with CD and those with NCGS.We compared clinical, neurophysiological, and imaging data of patients with CD and NCGS presenting with neurological dysfunction assessed and followed up regularly over a period of 20 years.Out of 700 patients, 562 were included. Exclusion criteria included no bowel biopsy to confirm CD, no HLA type available, and failure to adhere to GFD. All patients presented with neurological dysfunction and had circulating anti-gliadin antibodies. Out of 562 patients, 228 (41%) had evidence of enteropathy (Group 1, CD) and 334 (59%) did not (Group 2, NCGS). The most common neurological manifestations were cerebellar ataxia, peripheral neuropathy, and encephalopathy. There was a greater proportion of patients with encephalopathy in Group 1 and with a greater proportion of neuropathy in Group 2. The severity of ataxia did not differ between the two groups. Patients in Group 1 had more severe neuropathy. All patients from both groups responded to gluten-free diet. Anti-tissue transglutaminase (TG2) antibodies were found in 91% of patients in Group 1 and in 29% of patients in Group 2. Comparison between those patients in Group 2 with HLA-DQ2/DQ8 and those without as well as those with positive TG2 compared with those with negative TG2 antibodies identified no differences within these subgroups. Serological positivity for TG6 antibodies was similar in the two groups (67 and 60%).The neurological manifestations of CD and NCGS are similar and equally responsive to a GFD suggestive of common pathophysiological mechanisms.

Project description:BackgroundThere is an unmet need for novel treatments, such as drugs or vaccines, adjunctive to or replacing a burdensome life-long gluten-free diet for coeliac disease. The gold standard for successful treatment is a healed small intestinal mucosa, and therefore, the outcome measures in proof-of-concept studies should be based on evaluation of small intestine biopsies. We here evaluated morphometric, immunohistochemical and messenger RNA (mRNA) expression changes in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded biopsies.MethodsFifteen coeliac disease patients were challenged with 4 g of gluten per day for 10 weeks and 24 non-coeliac patients served as disease controls. A wide array of histological and immunohistochemical staining and mRNA-based gene expression tests (RT-qPCR and RNAseq) were carried out.ResultsDigital quantitative villous height: crypt depth ratio (VH: CrD) measurements revealed significant duodenal mucosal deterioration in all coeliac disease patients on gluten challenge. In contrast, the Marsh-Oberhuber class worsened in only 80% of coeliac patients. Measuring the intraepithelial CD3+ T-lymphocyte and lamina propria CD138+ plasma cell densities simultaneously proved to be a meaningful new measure of inflammation. Stainings for γδ T cells and IgA deposits, where previously frozen samples have been needed, were successful in PAXgene fixed paraffin-embedded samples. Messenger RNA extraction from the same paraffin-embedded biopsy block was successful and allowed large-scale qRT-PCR and RNAseq analyses for gene expression. Molecular morphometry, using the mRNA expression ratio of villous epithelium-specific gene APOA4 to crypt proliferation gene Ki67, showed a similar significant distinction between paired baseline and post-gluten challenge biopsies as quantitative histomorphometry.ConclusionRigorous digitally measured histologic and molecular markers suitable for gluten challenge studies can be obtained from a single paraffin-embedded biopsy specimen. Molecular morphometry seems to be a promising new tool that can be used in situations where assessing duodenal mucosal health is of paramount importance. In addition, the diagnostically valuable IgA deposits were now stained in paraffin-embedded specimens making them more accessible in routine clinics.

Project description:ObjectivesTo determine the prevalence of food insecurity among individuals with coeliac disease (CeD) and non-coeliac gluten sensitivity (NCGS) in the Netherlands and explore its association with diet quality and other barriers to adherence to a gluten-free diet.DesignMixed-method design comprising a survey and semistructured interviews.SettingAn online survey was distributed through social media accounts and the newsletter of the Dutch Association for Celiac Disease. Community-dwelling patients were surveyed and interviewed between June and November 2023.Participants and outcome measuresIn total 548 adults with CeD and NCGS in the Netherlands who adhered to a gluten-free diet completed the survey including questions related to demographics, household food insecurity, financial stress and diet quality. Regression analyses were conducted to assess associations between food insecurity and diet quality, and between food insecurity and perceived difficulty of gluten-free eating and cooking. Additionally, semistructured interviews with eight food insecure adults with CeD were conducted.ResultsThe prevalence of food insecurity was 23.2%, with 10.4% reporting very low food security. Very low food insecurity was associated with poorer diet quality (β=-5.5; 95% CI=-9.2 to -1.9; p=0.003). Food insecurity was associated with heightened perceived barriers across multiple themes. In age, income and education adjusted models, compared with food secure participants, low food secure participants were more likely to experience difficulty regarding skills (OR=2.5; 95% CI=1.5 to 4.3; p≤0.001), social circumstances (OR=2.6; 95% CI=1.1 to 6.4; p=0.038), resources (OR=2.5; 95% CI=1.5 to 4.4; p=0.001) and naturally gluten-free products (OR=1.8; 95% CI=1.0 to 3.1; p=0.045) in gluten-free eating and cooking. Participants with very low food security were more likely to experience difficulty regarding skills (OR=4.4; 95% CI=2.4 to 8.1; p≤0.001) and resources (OR=4.2; 95% CI=2.3 to 7.8; p<0.001) in gluten-free eating and cooking. The qualitative analysis provided a deeper understanding of these challenges, including employed strategies to manage costs and insights into the mental burden associated with adhering to a gluten-free diet.ConclusionThese findings indicate that food insecurity is prevalent among Dutch people with CeD and NCGS, with potential impact on diet quality and adherence to a gluten-free diet. It further provided insight into perceived barriers to adhering to a gluten-free diet among this target population. These challenges should be taken into account by clinicians and policy makers.

Dataset Information

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

Publications

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

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