The Metabonomic Signature of Celiac Disease

Abstract

Celiac disease (CD) is a multifactorial disorder involving genetic and environmental factors, thus, having great potential impact on metabolism. This study aims at defining the metabolic signature of CD through Nuclear Magnetic Resonance (NMR) of urine and serum samples of CD patients. Thirty-four CD patients at diagnosis and 34 healthy controls were examined by (1)H NMR of their serum and urine. A CD patients' subgroup was also examined after a gluten-free diet (GFD). Projection to Latent Structures provided data reduction and clustering, and Support Vector Machines provided pattern recognition and classification. The classification accuracy of CD and healthy control groups was 79.7-83.4% for serum and 69.3% for urine. Sera of CD patients were characterized by lower levels (P < 0.01) of several metabolites such as amino acids, lipids, pyruvate and choline, and by higher levels of glucose and 3-hydroxybutyric acid, while urines showed altered levels (P < 0.05) of, among others, indoxyl sulfate, meta-[hydroxyphenyl]propionic acid and phenylacetylglycine. After 12 months of GFD, all but one of the patients were classified as healthy by the same statistical analysis. NMR thus reveals a characteristic metabolic signature of celiac disease. Altered serum levels of glucose and ketonic bodies suggest alterations of energy metabolism, while the urine data point to alterations of gut microbiota. Metabolomics may thus provide further hints on the biochemistry of the disease.

Are Patients with Potential Celiac Disease Really Potential? The Answer of Metabonomics

“…Even though minor differences are present (due to the different data set and slightly different statistical analysis), this pattern is coherent with the previous work and corroborates the previous findings. 14 Comparing the serum spectra of overt CD with those of potential CD, we find that potential CD patients are characterized by lower levels of dimethylglycine and higher levels of glutamate and lipids (P < 0.05); no other metabolites are found significantly different in serum. In urine, more differences are found, in particular potential CD patients shows lower levels of glutamate/glutamine, IS, mHPPA, PAG, p-cresolsulfate, and citrate (see Table 3).…”

“…The present work classifies potential CD subjects (29) on the basis of a learning set of controls and CD subjects that has been considerably expanded with respect to the previous study 14 (61 + 51). The global accuracy obtained in discriminating nonceliac control subjects and patients is good enough (81.2%) to allow us to try to make predictions about the metabolic status of potential CD subjects.…”

“…Therefore, for ethical reasons, the 34 controls that were from the medical staff did not undergo intestinal biopsy; in the remaining 17 cases, gastrointestinal endoscopy was performed only when it was considered necessary to the diagnosis. The clinical characteristics of all the subjects, including those examined in the previous work 14 are reported in Supporting Table S1.…”

“…10 In a recent work, Bertini et al have examined a cohort of CD patients, before and after gluten free diet GDF, and healthy controls, by 1 H NMR metabolic profiling of their serum and urine samples. 14 Through multivariate analysis, they were able to demonstrate the existence of a clear metabonomic 15 signa-ture of CD and to identify a number of serum and urine metabolites whose levels were significantly different in CD at diagnosis as compared to controls. The metabonomic signature as well the levels of most metabolites reverted to normal within 12 months of a strict GFD.…”

Magnetic Resonance Spectroscopy: Principles and Techniques: Lessons for Clinicians

“…[23][24][25] Comprehensive metabolic profiles have been generated from biofluids including urine, serum, bile and intact tissue. 24,[26][27][28][29][30][31][32] …”