Is Gluten the Culprit in Non-Celiac Gluten Sensitivity?

Rapidly fermented poorly absorbed short-chain carbohydrates, rather than gluten or other wheat proteins, might cause gastrointestinal symptoms in people who do not have celiac disease but feel better on gluten-free diets, according to the August issue of Gastroenterology.

Individuals with non-celiac gluten sensitivity (NCGS), do not have celiac disease (based on serologic, allergy, and endoscopic analyses), but develop irritable bowel syndrome-like symptoms after ingestion of gluten—these symptoms are reduced after gluten is withdrawn from the diet.

Oat topped whole grain bread.

The symptoms of NCGS are intestinal (diarrhea, abdominal discomfort or pain, bloating, and flatulence) and extra-intestinal (headache, lethargy, poor concentration, ataxia, and oral ulcers).

Based on these criteria, physicians have considered NCGS to be a subset of irritable bowel syndrome or a closely related but distinct functional disorder. Although NCGS has been slowly recognized by physicians and scientists, the disorder has been rapidly adopted by the public—more than 20% of the general population reports symptoms following the ingestion of gluten.

There have been many studies of NCGS, yet there has been no agreement about what NCGS is (or is not), what causes it, and who it affects. It’s not even clear if gluten is the culprit in NCGS—other wheat proteins or carbohydrates could cause gastrointestinal symptoms in otherwise healthy individuals who eat wheat.

To help identify the factors that contribute to NCGS, Biesiekierski et al. performed a double-blind controlled trial of 37 subjects with NCGS. All participants were on gluten-free diets and remained on these for the first week of the study. They then spent 2 weeks on diets with reduced levels of fermentable oligo-, di-, and mono-saccharides and polyols (FODMAPs).

FODMAPs are poorly absorbed short-chain carbohydrates found in many foods that have become part of the Western diet. Due to their small size and rapid fermentability, they can distend the intestinal lumen with liquid and gas, and cause symptoms in people with visceral hypersensitivity or abnormal motility responses.

After 2 weeks on the low-FODMAP diets, participants were randomly assigned to groups that were placed on high-gluten (16 g gluten per day), low-gluten (2 g gluten per day and 14 g whey protein per day), or control (16 g whey protein per day) diets for 1 week, followed by a washout period of 2 weeks. Participants then crossed over to a different diet group and repeated this a third time until all participants had received all 3 diets.

Surprisingly, the gastrointestinal symptoms of the participants consistently and significantly improved during reduced intake of FODMAPs, but there was no evidence for symptomatic or biologic effects of gluten.

The authors conclude that NCGS, as currently defined, might not be a discrete entity (or its effects might be confounded by FODMAP restriction), and that gluten might not cause functional gut symptoms once dietary FODMAPs are reduced.

In an editorial that accompanies the article, Rohini Vanga and Daniel A. Leffler state that this study calls into question the very existence of NCGS as a discrete entity and suggests that reduction of FODMAPs, rather than gluten or other wheat proteins, might be mechanism by which low-gluten diets improve gastrointestinal symptoms.

Vanga and Leffler say that large trials are needed to investigate the role of specific diets in patients with chronic gastrointestinal symptoms. Studies are also needed to determine mechanisms and potential biomarkers of NCGS and other food sensitivities.

More Information on Celiac Disease and NCGS:

Read the article online
Biesiekierski JR, Peters SL, Newnham ED, et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology 2013;145:320-328.e3.

Read the accompanying editorial
Vanga R and Leffer DA. Gluten sensitivity: not celiac and not certain. Gastroenterology 2013;145:276-279.

About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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