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Non-Celiac Gluten Sensitivity Research - Next Steps Involve Proven Tests


Updated January 25, 2013

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

'Potential' Celiac Patients Share Distinctive Metabolic Fingerprint with Celiacs

There's other research indicating some people labeled "gluten-sensitive" may in fact have early-stage celiac disease.

A study published in the December 2010 Journal of Proteome Research finds that "potential" celiac patients with positive blood tests but negative biopsies actually have the same distinctive metabolic fingerprint as diagnosed celiacs. These "gluten-sensitive" people may simply represent an earlier stage of the condition, before it causes major damage to the intestines, the researchers said.

The study used magnetic resonance metabolic profiling to analyze biochemical markers in the urine and blood of 141 patients: 61 with diagnosed celiac disease, 29 with positive blood tests but negative biopsies, and 51 healthy controls.

They found that those with so-called "potential" celiac disease shared the same biochemical profile as diagnosed celiacs, while the biochemical profiles of the healthy controls differed markedly.

"Our results demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of GFD [gluten-free diet] in patients with potential CD [celiac disease]," the study concluded.

Gluten Sensitivity Probable in Patients with Borderline Biopsies

Another study looked at patients with celiac disease symptoms whose intestinal biopsies revealed only minor abnormalities, such as Marsh I or II lesions.

Many physicians will not diagnose celiac disease unless intestinal damage reaches Marsh III or Marsh IV levels.

In this study, 35 patients had low-level damage and were advised to follow a gluten-free diet anyway. Only 23 patients adhered to the diet, and the researchers took follow-up biopsies from everyone following the diet after eight to 12 months.

All 23 patients who followed the diet had a "dramatic clinical improvement in symptoms," and most saw complete or partial healing of their intestinal villi.

Seven of the 11 patients who refused to follow the gluten-free diet were evaluated eight to 12 months later, as well. Of these, six had unchanged symptoms and intestinal damage, and again declined to start a gluten-free diet. One saw increased damage in his intestinal villi (from Marsh I to Marsh IIIa), and opted to start the diet.

The study's authors concluded that the patients who didn't meet the criteria for celiac disease nonetheless were clearly gluten sensitive and benefited from the gluten-free diet.

"Although Marsh I-II lesions cannot be classified as celiac lesions, the patients' symptoms at presentation and the clear improvement of symptoms when on GFD [gluten-free diet], with or without improvement of histologic lesions, supports the assumption that these patients are sensitive to gluten and may justify treatment with a GFD," the researchers concluded.

Gluten Sensitivity May Affect One in 14 People

Gluten sensitivity (or intolerance) may affect about 6% to 7% of the population, according to Dr. Fasano. Others in the medical community have placed the percentage of gluten-intolerant people higher — I've seen estimates ranging from 10% to a mammoth 50% of the population.

Read more on these numbers: How Many People Have Gluten Sensitivity?

It's impossible to tell how many people actually have gluten sensitivity without more research and accepted gluten sensitivity tests. But clearly, even if the numbers are on the low side, they'll dwarf the number of celiacs, who make up about 1% of the population.

Many in the celiac/gluten-sensitive community believe that diseases caused by gluten array themselves on a "spectrum" of gluten-related conditions, with celiac disease, gluten ataxia (neurological damage from gluten) and gluten sensitivity all falling somewhere on that spectrum.

Dr. Fasano says the next step is the identification of a biological marker, or "biomarker," for gluten sensitivity. The clinical trial to do just that is underway right now, and Dr. Fasano says he's "confident" researchers will pinpoint that biomarker. From there, researchers can develop a test to detect gluten sensitivity — that could be available commercially within the next several years.


Bernini P. et al. Are Patients with Potential Celiac Disease Really Potential? The Answer of Metabonomics. Journal of Proteome Research. Published online Nov. 19, 2010. DOI: 10.1021/pr100896s.

J. Biesiekierski et al. Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial. American Journal of Gastroenterology advance online publication, Jan. 11, 2011; doi:10.1038/ajg.2010.487.

A. Fasano et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Medicine 2011, 9:23. doi:10.1186/1741-7015-9-23.

Fasano A. et. al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Medicine. BMC Medicine 2012, 10:13 doi:10.1186/1741-7015-10-13. Published: 7 February 2012

Tursi A. et al. The symptomatic and histologic response to a gluten-free diet in patients with borderline enteropathy. Journal of Clinical Gastroenterology. 2003 Jan; 36(1):6-7.

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