Alterations in One-Carbon Metabolism in Celiac Disease

Martín-Masot, Rafael; Mota‐Martorell, Natàlia; Jové, Mariona; Maldonado, J.; Pamplona, Reinald; Nestares, Teresa

doi:10.3390/nu12123723

Cited by 13 publications

(20 citation statements)

References 39 publications

(68 reference statements)

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“…Remarkably, 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]. In this study, a down-regulation of the trans-sulphuration pathway in CD patients was observed, in particular.…”

Section: Introductionsupporting

confidence: 76%

“…Effectively, available evidence from metabolomic studies certified the presence of minor but significant differences in the metabolic profile between healthy individuals and celiac patients (children and adults) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. In these studies, using NMR or MS-based methods, biological samples from different origins including faecalis material, plasma, serum, and urine were analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…In these studies, using NMR or MS-based methods, biological samples from different origins including faecalis material, plasma, serum, and urine were analyzed. Overall, the metabolomic changes described are associated with modifications in gut microflora and/or intestinal permeability, malabsorption, and alterations in metabolism [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Thus, lower concentrations of amino acids (asparagine, isoleucine, methionine, proline, and valine); diverse metabolites (choline, creatinine, lactate, lipids (phosphatidylcholines), methylamine, methylglutarate, and pyruvate); and higher levels of 3-hydroxybutyric acid, glucose, and triacyl glycerides were the main differences observed in the serum metabolome between CD subjects and healthy controls [ 11 , 12 , 13 , 14 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, lower concentrations of amino acids (asparagine, isoleucine, methionine, proline, and valine); diverse metabolites (choline, creatinine, lactate, lipids (phosphatidylcholines), methylamine, methylglutarate, and pyruvate); and higher levels of 3-hydroxybutyric acid, glucose, and triacyl glycerides were the main differences observed in the serum metabolome between CD subjects and healthy controls [ 11 , 12 , 13 , 14 , 15 , 16 ]. It is also particularly remarkable that the decreased levels of choline, methionine, and phosphatidylcholines [ 15 , 16 ] along with the decreased content of metabolites in the trans-sulphuration pathway [ 17 ] clearly suggest defects in the one-carbon metabolism in CD. Importantly, these studies also verified that the introduction of a strict GFD seems to quasi completely reverse the metabolic profile of CD subjects to the healthy condition.…”

Section: Discussionmentioning

confidence: 99%

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Up-Regulation of Specific Bioactive Lipids in Celiac Disease

et al. 2021

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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.

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Section: Introductionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Up-Regulation of Specific Bioactive Lipids in Celiac Disease

et al. 2021

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“…However, targeted metabolomic analysis investigating differences in the plasma choline/methionine metabolome of CD subjects were not reported. Only one study [ 81 ] in 17 children with CD, treated with a GFD, and 17 healthy control siblings has recently demonstrated the persistence of defects in the trans-sulfuration pathway of CD, despite dietary treatment. Conversely, choline metabolism seem to be preserved [ 81 ], a finding that might add further support to the results of the present study.…”

Section: Discussionmentioning

confidence: 99%

Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease

Lanza

Fisicaro

D’Agate³

et al. 2021

PLoS ONE

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Background Celiac disease (CD) is now viewed as a systemic disease with multifaceted clinical manifestations. Among the extra-intestinal features, neurological and neuropsychiatric symptoms are still a diagnostic challenge, since they can precede or follow the diagnosis of CD. In particular, it is well known that some adults with CD may complain of cognitive symptoms, that improve when the gluten-free diet (GFD) is started, although they may re-appear after incidental gluten intake. Among the neurophysiological techniques, motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) can non-invasively probe in vivo the excitation state of cortical areas and cortico-spinal conductivity, being also able to unveil preclinical impairment in several neurological and psychiatric disorders, as well as in some systemic diseases affecting the central nervous system (CNS), such as CD. We previously demonstrated an intracortical disinhibition and hyperfacilitation of MEP responses to TMS in newly diagnosed patients. However, no data are available on the central cholinergic functioning indexed by specific TMS measures, such as the short-latency afferent inhibition (SAI), which might represent the neurophysiological correlate of cognitive changes in CD patients, also at the preclinical level. Methods Cognitive and depressive symptoms were screened by means of the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively, in 15 consecutive de novo CD patients and 15 healthy controls. All patients were on normal diet at the time of the enrolment. Brain computed tomography (CT) was performed in all patients. SAI, recorded at two interstimulus intervals (2 and 8 ms), was assessed as the percentage amplitude ratio between the conditioned and the unconditioned MEP response. Resting motor threshold, MEP amplitude and latency, and central motor conduction time were also measured. Results The two groups were comparable for age, sex, anthropometric features, and educational level. Brain CT ruled out intracranial calcifications and clear radiological abnormalities in all patients. Scores at MoCA and HDRS were significantly worse in patients than in controls. The comparison of TMS data between the two groups revealed no statistically significant difference for all measures, including SAI at both interstimulus intervals. Conclusions Central cholinergic functioning explored by the SAI of the motor cortex resulted to be not affected in these de novo CD patients compared to age-matched healthy controls. Although the statistically significant difference in MoCA, an overt cognitive impairment was not clinically evident in CD patients. Coherently, to date, no study based on TMS or other diagnostic techniques has shown any involvement of the central acetylcholine or the cholinergic fibers within the CNS in CD. This finding might add support to the vascular inflammation hypothesis underlying the so-called “gluten encephalopathy”, which seems to be due to an aetiology different from that of the cholinergic dysfunction. Longitudinal studies correlating clinical, TMS, and neuroimaging data, both before and after GFD, are needed.

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One carbon metabolism and its implication in health and immune functions

Dang,

Jain,

Dhanda

et al. 2024

Cell Biochemistry & Function

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One carbon (1C) metabolism is critical for cellular viability and physiological homeostasis. Starting from its crucial involvement in purine biosynthesis to posttranslational modification of proteins, 1C metabolism contributes significantly to the development and cellular differentiation through methionine and folate cycles that are pivotal for cellular function. Genetic polymorphisms of several genes of these pathways are implicated in disease pathogenesis and drug metabolism. Metabolic products of 1C metabolism have significant roles in epigenetic modifications through DNA and histone protein methylation. Homocysteine is a product that has clinical significance in the diagnosis and prognosis of several critical illnesses, including chronic immune diseases and cancers. Regulation of the function and differentiation of immune cells, including T‐cells, B‐cells, macrophages, and so forth, are directly influenced by 1C metabolism and thus have direct implications in several immune disease biology. Recent research on therapeutic approaches is targeting nuclear, cytoplasmic, and mitochondrial 1C metabolism to manage and treat metabolic (i.e., type 2 diabetes), neurodegenerative (i.e., Alzheimer's disease), or immune (i.e., rheumatoid arthritis) diseases. 1C metabolism is being explored for therapeutic intervention as a common determinant for a spectrum of immune and metabolic diseases. Identifying the association or correlation between essential metabolic products of this pathway and disease onset or prognosis would further facilitate the clinical monitoring of diseases.

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Alterations in One-Carbon Metabolism in Celiac Disease

Cited by 13 publications

References 39 publications

Up-Regulation of Specific Bioactive Lipids in Celiac Disease

Up-Regulation of Specific Bioactive Lipids in Celiac Disease

Preserved central cholinergic functioning to transcranial magnetic stimulation in de novo patients with celiac disease

One carbon metabolism and its implication in health and immune functions

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