Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.

Related collections

Most cited references 36

Record: found
Abstract: found
Article: not found

No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.

Jessica Biesiekierski, Simone L. Peters, Evan Newnham … (2013)

Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease but their symptoms improve when they are placed on gluten-free diets. We investigated the specific effects of gluten after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates (fermentable, oligo-, di-, monosaccharides, and polyols [FODMAPs]) in subjects believed to have NCGS. We performed a double-blind cross-over trial of 37 subjects (aged 24-61 y, 6 men) with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease. Participants were randomly assigned to groups given a 2-week diet of reduced FODMAPs, and were then placed on high-gluten (16 g gluten/d), low-gluten (2 g gluten/d and 14 g whey protein/d), or control (16 g whey protein/d) diets for 1 week, followed by a washout period of at least 2 weeks. We assessed serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants then crossed over to groups given gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days. Symptoms were evaluated by visual analogue scales. In all participants, gastrointestinal symptoms consistently and significantly improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein. Gluten-specific effects were observed in only 8% of participants. There were no diet-specific changes in any biomarker. During the 3-day rechallenge, participants' symptoms increased by similar levels among groups. Gluten-specific gastrointestinal effects were not reproduced. An order effect was observed. In a placebo-controlled, cross-over rechallenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

0 comments Cited 252 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.

Jessica Biesiekierski, Evan Newnham, Peter M Irving … (2011)

Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.

0 comments Cited 203 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders.

Paul Shattock, Judith Jacobsen, Paul Whiteley … (2010)

There is increasing interest in the use of gluten- and casein-free diets for children with autism spectrum disorders (ASDs). We report results from a two-stage, 24-month, randomised, controlled trial incorporating an adaptive 'catch-up' design and interim analysis. Stage 1 of the trial saw 72 Danish children (aged 4 years to 10 years 11 months) assigned to diet (A) or non-diet (B) groups by stratified randomisation. Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) were used to assess core autism behaviours, Vineland Adaptive Behaviour Scales (VABS) to ascertain developmental level, and Attention-Deficit Hyperactivity Disorder - IV scale (ADHD-IV) to determine inattention and hyperactivity. Participants were tested at baseline, 8, and 12 months. Based on per protocol repeated measures analysis, data for 26 diet children and 29 controls were available at 12 months. At this point, there was a significant improvement to mean diet group scores (time*treatment interaction) on sub-domains of ADOS, GARS and ADHD-IV measures. Surpassing of predefined statistical thresholds as evidence of improvement in group A at 12 months sanctioned the re-assignment of group B participants to active dietary treatment. Stage 2 data for 18 group A and 17 group B participants were available at 24 months. Multiple scenario analysis based on inter- and intra-group comparisons showed some evidence of sustained clinical group improvements although possibly indicative of a plateau effect for intervention. Our results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD. In the absence of a placebo condition to the current investigation, we are, however, unable to disqualify potential effects derived from intervention outside of dietary changes. Further studies are required to ascertain potential best- and non-responders to intervention. The study was registered with ClincialTrials.gov, number NCT00614198.

0 comments Cited 79 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 26 September 2013

Publication date Collection: October 2013

Volume: 5

Issue: 10

Pages: 3839-3853

Affiliations

[1 ]Department of Pediatrics, Università Politecnica delle Marche, Ancona 60121, Italy; E-Mail: catassi@ 123456tin.it

[2 ]Departamento de Medicina, Hospital de Gastroenterología “Dr. Carlos Bonorino Udaondo”, Buenos Aires 1264, Argentina; E-Mail: jbai@ 123456intramed.net

[3 ]Department of Gastroenterology and Liver Diseases, CHU Grenoble 38043, France; E-Mail: bbonaz@ 123456chu-grenoble.fr

[4 ]Department of Gastroenterology and Hepatology, Vrije Universiteit Medical Center, Amsterdam 1081 HV, The Netherlands; E-Mail: g.bouma@ 123456vumc.nl

[5 ]Gastroenterology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence 50134, Italy; E-Mail: a.calabro@ 123456dfc.unifi.it

[6 ]Department of Internal Medicine, “Giovanni Paolo II” Hospital, Sciacca (AG) and University of Palermo, Sciacca 92019, Italy; E-Mail: acarroccio@ 123456hotmail.com

[7 ]Pediatric Gastroenterology Unit, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Tarragona 43204, Spain; E-Mail: gcv@ 123456tinet.cat

[8 ]Department of Medicine and Surgery, University of Salerno, Baronissi Campus, Salerno 84081, Italy; E-Mail: cciacci@ 123456unisa.it

[9 ]Interdisciplinary Department of Medicine, University of Bari, Bari 70124, Italy; E-Mails: fernandacristofori@ 123456gmail.com (F.C.); rfrancavilla@ 123456gmail.com (R.F.)

[10 ]Gastroenterology Unit, Department of Pediatrics, University Medical Centre Maribor, Maribor 2000, Slovenia; E-Mail: jernej.dolinsek@ 123456ukc-mb.si

[11 ]Centro Prevenzione e Diagnosi Malattia Celiaca Fondazione IRCCS Ca Granda, Milan 20122, Italy; E-Mail: lucelli@ 123456yahoo.com

[12 ]Department of Medicine, Celiac Disease Center, Columbia University Medical Center, New York, NY 10032, USA; E-Mail: pg11@ 123456columbia.edu

[13 ]Division of Gastroenterology and Internal Medicine, Hospital Porz am Rhein, Köln 51149, Germany; E-Mail: w.holtmeier@ 123456khporz.de

[14 ]German Research Center for Food Chemistry, Leibniz Institute, Freising 85354, Germany; E-Mail: peter.koehler@ 123456tum.de

[15 ]Division of Pediatric Gastroenterology and Hepatology, Dr. von Hauner Children’s Hospital, University of Munich Medical Center, Munich 80337, Germany; E-Mail: sybille.koletzko@ 123456med.uni-muenchen.de

[16 ]Practice of Nutrition Therapy Meinhold & Team, Köln 50674, Germany; E-Mail: praxis@ 123456christof-meinhold.de

[17 ]Department of Gastroenterology and Hepatology, Royal Hallamshire Hospital and University of Sheffield Medical School, Sheffield S10 2JF, UK; E-Mail: david.sanders@ 123456sth.nhs.uk

[18 ]Department of Gastroenterology, Rheumatology and Infectiology, Charité University Medicine, Berlin 10203, Germany; E-Mails: michael.schumann@ 123456charite.de (M.S.); reiner.ullrich@ 123456charite.de (R.U.)

[19 ]Department of Medicine I, University Medical Center, Johannes Gutenberg University Mainz, Mainz 55131, Germany; E-Mails: dschuppa@ 123456bidmc.harvard.edu (D.S.); zevallos@ 123456uni-mainz.de (V.Z.)

[20 ]Division of Gastroenterology and Celiac Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA

[21 ]St. Anna Children’s Hospital, Vienna 1090, Austria; E-Mail: andreas.vecsei@ 123456stanna.at

[22 ]Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy; E-Mail: uvolt@ 123456yahoo.com

[23 ]Department of Gastroenterology, Second University of Naples, Naples 80136, Italy; E-Mail: annasapone@ 123456yahoo.it

[24 ]Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Boston, MA 02129, USA

Author notes

[* ] Author to whom correspondence should be addressed; E-Mail: afasano@ 123456partners.org ; Tel.: +1-617-726-1450.

Article

Publisher ID: nutrients-05-03839

DOI: 10.3390/nu5103839

PMC ID: 3820047

PubMed ID: 24077239

SO-VID: 3d88a978-9698-4118-8859-31e63d955541

License:

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

History

Date received : 20 August 2013

Date revision received : 17 September 2013

Date accepted : 18 September 2013

Comments

Comment on this article

scite_

Cited by 142

See all cited by

- Version 1

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

Read this article at

Abstract

Related collections

Karger: Nutrition and Dietetics

Most cited references 36

No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.

Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.

The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 226

Cited by 142