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

Abstract

Celiac disease (CD) is an autoimmune disorder caused by a permanent sensitivity to gluten in genetically susceptible individuals. Accurate diagnosis of CD at an early stage and its treatment with a gluten-free diet (GFD) are important for optimum treatment and prognosis. Recently, by employing a noninvasive metabonomic approach, we have shown that CD has a well-defined metabonomic signature. Here we address potential CD patients, defined as subjects who do not have, and have never had, a jejunal biopsy consistent with clear CD, and yet have immunological abnormalities similar to those found in celiac patients. Sixty-one overt CD patients at diagnosis, 29 patients with potential CD, and 51 control subjects were examined by 1 H NMR of their serum and urine: out of 29 potential CD patients, 24 were classified as CD and 5 as control subjects. Potential CD largely shares the metabonomic signature of overt CD. Most metabolites found to be significantly different between control and CD subjects were also altered in potential CD. 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 in patients with potential CD, as recently suggested by prospective clinical studies.

Metabolomic NMR Fingerprinting to Identify and Predict Survival of Patients with Metastatic Colorectal Cancer

“…Metabolomics is a post-genomic research field concerned with the study of metabolic profiles in biologic samples such as isolated cells (4), tissues (5) or body fluids (6)(7)(8)(9)(10). In recent years, metabolomic studies have provided a significant contribution to the detailed understanding of the biochemical network and pathways in oncology (11), highlighting the potential of metabolomic analyses of blood samples for the detection of cancers, including epithelial ovarian (12), leukemia (13), oral (14), breast (15,16), prostate (11), liver (17) as well as colorectal cancer (CRC; refs.…”

Investigating the early metabolic fingerprint of celiac disease – a prospective approach

“…Some publications focus on the metabolic fingerprint for CD in one of the matrices serum, urine, or gut microbiota, but they compare CD patients (potential or overt) with healthy controls [14,15]. Their design differs from ours in that it is cross sectional rather than prospective.…”

“…Bernini et al [15] put emphasis on the precondition of CD and compared healthy subjects with those having potential or overt CD. Potential CD patients, having the typical immunological features of clear CD in the absence of any apparent intestinal damage, were found to have a virtually similar metabolic profile as the patients with overt CD.…”

“…So far, only few studies investigated the differences in metabolic profiles between CD patients and healthy controls [13], and even fewer studies focused on the serum metabolic profile. The results of those studies, however, 6 are quite promising revealing alterations in energy metabolism [14] and suggesting that metabolic alterations may precede the development of small intestinal villous atrophy [15].…”

Biomarkers and the Future of Pediatric Gastroenterology

“…Other examples of pediatric gastrointestinal diseases that may be better understood using metabolites as disease markers are infantile colic, with elevated urinary 5-hydroxy indole acetic acid (a serotonin metabolite) [9] and celiac disease, which is characterized metabolically by reduced serum citrulline, choline, creatinine, branch chain amino acids and lipids [10]. These markers appear to be abnormal even before onset of the disease.…”