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Metabonomic Signature of Celiac Disease
Celiac.com 12/23/2008 - Metabolites are small–molecule products of biochemical processes in the body’s cells. Analysis of these metabolites can detect changes in the body caused by chemical toxicity, disease, gene mutations, or diet. Bacteria in the gut also contribute to this “metabolic signature”, so it is also a way to understand changes in gut microbe populations.
Because metabolites are excreted from the cells into blood and urine, collecting these samples can be easy, noninvasive, and inexpensive. Chemical techniques like nuclear magnetic resonance (NMR) spectroscopy are used to analyze the samples. The results of NMR spectroscopy are chemical patterns, showing the simultaneous alterations of many compounds. The measurement and analysis of multiple metabolite changes in response to genetic changes or environmental stimuli is known as metabonomics.
Metabonomics has a number of potential applications. Ease of sample collection may enable researchers to develop a rapid screening tool for diseases like celiac disease. Using metabonomics, it is not necessary to know the specific metabolites that differ in people with a given disease (the disease biomarkers). Rather than looking for the presence or absence of a particular biomarker, the overall pattern of metabolite concentrations is compared to patterns of people known to have the disease (the metabolic signature of the disease) and patterns of people who do not have the disease. Large numbers of metabolites are analyzed simultaneously, instead of one by one, providing a snapshot into what is happening in the cells at a given time.
In this first study to investigate the metabonomic signature of celiac disease, blood and urine samples of 34 people with celiac disease were analyzed at the time of diagnosis, which was based on antibody tests and confirmed with biopsies of the small intestine. These patterns were compared to the metabolite patterns of 34 people without celiac disease. Using blood samples, researchers were able to predict celiac disease up to 83% of the time. Analysis of urine samples gave accuracy of about 70%.
These accuracy rates are lower than those achieved with antibody tests, but this is only the first small study and refining the techniques may significantly improve accuracy rates. In addition, analyzing the metabolic signature may lead to a greater understanding of celiac disease and the cause of its various symptoms. For example, results from this study included lower levels of some metabolites such as pyruvate (a product of glucose breakdown) coupled with elevated levels of other metabolites such as glucose and 3-hydroxybutyric acid (a by-product of fat breakdown) in people with celiac disease.
These results suggest a possible explanation for chronic fatigue experienced by up to 87% of patients with celiac disease—a possible impairment in the body’s ability to use glucose for energy. As expected, evidence of altered gut bacteria was also found, as were an increase in metabolites that indicate an increased intestinal permeability (“leaky gut”). After 12 months of a strict gluten-free diet, these altered metabolite patterns reverted to normal.
Metabonomics is an emerging field of study, which like genomics, holds great promise in the understanding, diagnosis, and treatment of diseases like celiac disease.
Bertini I, et al. The metabonomic signature of celiac disease. Journal of Proteome Research. 2008 Dec 11 [Epub ahead of print]
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Kathleen La Point
Kathleen LaPoint is a biomedical writer with a B.S. in Molecular Biology and an M.S. in Bacteriology from the University of Wisconsin - Madison.View all articles by Kathleen La Point
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