Abstract
Celiac disease (CD) is an autoimmune enteropathy linked to alterations of metabolism. Currently, limited untargeted metabolomic studies evaluating differences in the plasma metabolome of CD subjects have been documented. We engage in a metabolomic study that analyzes plasma metabolome in 17 children with CD treated with a gluten-free diet and 17 healthy control siblings in order to recognize potential changes in metabolic networks. Our data demonstrates the persistence of metabolic defects in CD subjects in spite of the dietary treatment, affecting a minor but significant fraction (around 4%, 209 out of 4893 molecular features) of the analyzed plasma metabolome. The affected molecular species are mainly, but not exclusively, lipid species with a particular affectation of steroids and derivatives (indicating an adrenal gland affectation), glycerophospholipids (to highlight phosphatidic acid), glycerolipids (with a special affectation of diacylglycerols), and fatty acyls (eicosanoids). Our findings are suggestive of an activation of the diacylglycerol-phosphatidic acid signaling pathway in CD that may potentially have detrimental effects via activation of several targets including protein kinases such as mTOR, which could be the basis of the morbidity and mortality connected with untreated CD. However, more studies are necessary to validate this idea regarding CD.
Highlights
The variability in clinical manifestations of Celiac disease (CD) is due to the interindividual differential The variability in clinical manifestations of CD is due to the interindividual differenvulnerability supported by genetic, immunological, and environmental factors
Rethe diversity of signs and symptoms generated by CD, recent observations suggest that garding the diversity of signs and symptoms generated by CD, recent observations sugmetabolic alterations in subjects with CD must be considered
In cases nowadays the diagnosis of CD requires confirmation by a positive biopsy, a better most cases nowadays the diagnosis of CDunderlying requires confirmation bycould a positive biopsy, a understanding of the metabolic processes this pathology offer the opporbetter of the new metabolic processes underlying this pathology coulduseful offer the tunityunderstanding to uncover potential physiopathological mechanisms and biomarkers for opportunity to uncover potential new physiopathological mechanisms and biomarkers the diagnosis of doubtful cases due to the histological results as well as for follow-up of the disease
Summary
Differences in methionine, choline, and choline-derived lipids content in CD subjects were described, suggestive of an affectation of one-carbon metabolism. This alteration of methionine metabolism in CD subjects was recently confirmed and extended using a LC–MS/MS approach [17]. Its composition is under strict control despite the continuous change induced by different internal and external conditions in physiological and pathological states [19,20]. These facts allow us to ensure the identification of new molecular mechanisms and targets that may lead to healthier states. The plasma metabolome profile was defined using an LC–MS/MS platform to discriminate specific phenotypic patterns linked to genotypes of CD
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