NMR for celiac disease: metabonomic insights

Autoimmune issue

Celiac disease is a problem of the immune system that causes genetically susceptible people to have a permanent sensitivity to gluten composite. Gluten is the composite of a prolamin and a glutelin, are hooked up with starch in the endosperm of various grass-related grains, most infamously wheat, but also in barley and rye. Gluten is obviously found most commonly in food products made from these grains but may also be present in medicines, vitamin supplements and even lip balm, according to the US National Digestive Diseases Information Clearinghouse (NDDIC).

The autoimmune response to gluten in people with celiac disease causes damage to the ileum, the small intestine, whereby the tiny protrusions, the villi, which line the intestine and provide a large surface area for absorption, shrink, or atrophy. The intestinal inflammation seen in celiac disease might also simply lead to an increase in the number of white blood cells in so-called silent celiac disease patients.

Malabsorption and intestinal damage

Because of the potential for such developmental problems, an accurate diagnosis of celiac disease early in life is important. Treatment is not complex, although is sometimes difficult to sustain and involves nothing more sophisticated than ensure the individual has an entirely gluten-free diet. This is successful in the majority of patients and intestinal problems can be eradicated in this way; reintroduction of gluten into the diet will cause a relapse.

Now, Ivano Bertini, Magnetic Resonance Center (CERM), University of Florence, Italy and colleagues there and at the FiorGen Foundation, Tuscany Referral Center for Adult Celiac Disease, and the A. Meyer University Children?s Hospital have developed a non-invasive metabonomic approach to the diagnosis of celiac disease based on proton NMR spectroscopy. They found that the disorder produces a rather well-defined signature of metabolites and so can diagnose individuals who have not a biopsy taken from the jejunal section of the small intestine.

Testing serum, urine

"Most metabolites found to be significantly different between control and celiac disease subjects were also altered in potential celiac disease," the team says. "Our results demonstrate that metabolic alterations may precede the development of small intestinal villous atrophy and provide a further rationale for early institution of a gluten-free diet in patients with potential celiac disease, as recently suggested by prospective clinical studies." The team has demonstrated that the metabonomic signature as well the levels of most metabolites revert to normal within a year of adopting a strict gluten-free diet.

Intriguingly, the metabonomic fingerprint in celiac disease has two components essentially unrelated to malabsorption of nutrients. One is related to energy metabolism, and the other to alterations in gut microflora. Differences in these aspects of the metabolic fingerprint between celiac and non-celiac samples can allow predictions about celiac disease status to be made with reasonable accuracy (about 84%). Of course, clinically, it is possible achieve sensitivity of about 98% and specificity of more than 95% with standard blood tests and follow-up endoscopy for the physical elimination of false positives. But, the existence of a metabolic signature in serum and urine could be very important in quickly identifying silent, latent and potential celiac disease where there may be intestinal pathology but either no obvious celiac symptoms or else abnormalities that could emerge later.

Improved celiac understanding

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.