Metabolic abnormalities of gastrointestinal mucosa in celiac disease: An <i>in vitro</i> proton nuclear magnetic resonance spectroscopy study

Sharma, Uma; Upadhyay, Deepti; Mewar, Sujeet; Mishra, Abhishek; Das, Prasenjit; Gupta, Siddhartha Datta; Dwivedi, Sada Nand; Makharia, Govind; Jagannathan, Naranamangalam R.

doi:10.1111/jgh.12979

Cited by 18 publications

(23 citation statements)

References 26 publications

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“…Also the results suggested that elevated level of aspartate in intestinal mucosa may lead to deficiency of aspartate for urea cycle in liver and thus may contribute to liver abnormalities associated with CeD. Furthermore, the significantly higher concentrations of pyruvate and succinate in intestinal mucosa of patients with CeD in comparison to controls suggests abnormality in glycolysis metabolic pathway and Kreb's cycle, thus leading to energy deficiency in CeD [38].…”

Section: Intestinal Mucosamentioning

confidence: 88%

“…Recently, NMR based metabonomics approach using samples like urine, blood plasma/sera and mucosa samples showed putative biomarkers for the diagnosis of CeD [4,16,38]. These studies demonstrated that in-vitro high-resolution NMR spectroscopy may emerge as a promising tool for the evaluation of CeD through the analysis of intestinal mucosal biopsies, body fluids and faecal extracts.…”

Section: Upadhyay Et Al / Review: Role Of Nmr Metabonomics In Celmentioning

confidence: 99%

“…The lower levels of several metabolites such as amino acids (asparagine, isoleucine, methionine, proline, valine), pyruvate, creatinine, lipids, lactate, and choline, and increased levels of glucose and ketone bodies such as 3-hydroxybutyric acid were reported in the sera of CeD patients as compared to healthy controls [4]. The higher level of glucose and reduced level of pyruvate and lactate in sera of CeD patients Table 1 Metabolites [chemical shift position (δ) ppm] observed in the 1 H NMR spectrum of perchloric acid extract of intestinal mucosal biopsy [38], and blood [4] and urine [4] were due to impairment of glycolysis. Further, the sera of CeD patients is characterised with lower level of lipids which was attributed to enhanced lipid β-oxidation and malabsorption.…”

Section: Bloodmentioning

confidence: 99%

“…Till date there is only one in-vitro 1 H NMR study of intestinal mucosal biopsies in patients with CeD [38]. The study showed significantly higher concentration of several metabolites such as pyruvate, succinate, leucine, isoleucine and aspartate and decreased level of glycerophosphocholine in intestinal mucosa of patients with CeD in comparison to controls with non-CeD conditions such as dyspepsia and gastroesophageal reflux disease in whom intestinal mucosa appeared normal [38]. Elevated levels of amino acids in intestinal mucosa of patients with CeD may be due to decreased utilisation of amino acids as energy substrates.…”

Section: Intestinal Mucosamentioning

confidence: 99%

“…These include diarrhoea, abdominal distension, failure to thrive and fatigue in infants and children, anemia, metabolic bone disease, liver diseases and ataxia and these complicate its diagnosis [35]. Currently screening of CeD is based on the detection of serological markers such as endomysial (EMA) and tissue transglutaminase (tTG) IgA antibodies, however, confirmation of diagnosis of CeD is achieved only after comprehensive evaluation of clinical, serological, genetic and histological specimens.Recently, NMR based metabonomics approach using samples like urine, blood plasma/sera and mucosa samples showed putative biomarkers for the diagnosis of CeD [4,16,38]. These studies demonstrated that in-vitro high-resolution NMR spectroscopy may emerge as a promising tool for the evaluation of CeD through the analysis of intestinal mucosal biopsies, body fluids and faecal extracts.This review presents some salient features of pathophysiology of CeD and the experimental aspects of metabonomics studies using proton ( 1 H) NMR spectroscopy.…”

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confidence: 99%

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Role of NMR metabonomics in Celiac Disease (CeD)

Upadhyay

Sharma

Makharia

et al. 2017

BSI

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Metabonomics study provides a comprehensive metabolic profile of biological samples using techniques like mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. The metabolites identified are later analysed using multivariate statistical methods. Metabonomics has the potential to provide putative biomarker/s for disease diagnosis and for monitoring the disease progression and can be used in patient management. Recently, a few metabonomics studies have been reported on blood sera, urine and intestinal mucosal biopsies of celiac disease (CeD) patients using proton NMR. Significantly decreased levels of amino acids, methylamine, lactate, lipids, pyruvate, creatinine, choline and glycoprotein and increased levels of glucose and β-hydroxybutyrate have been reported in blood sera of CeD patients. In intestinal mucosal biopsies of CeD patients, a higher concentration of isoleucine, leucine, aspartate, succinate and pyruvate and lower concentration of glycerophosphocholine was seen as compared to controls. These studies indicates that the metabonomics study of CeD using in-vitro NMR spectroscopy helps in the determination of metabolic signature/s of the disease. It also provides an insight into the biochemistry of the disease and also helps in the identification of metabolites that could serve as putative biomarker/s for the diagnosis of CeD. This review focuses on the application of NMR based metabonomics in CeD and highlights the potential of NMR based metabonomics in the identification of biomarker/s for diagnosis and prognosis. (CeD) pathological conditions. NMR based metabonomics approach has been applied extensively in medicine for delineating metabolic signature/s of several diseases such as colonic tumors [28], fatty liver disease [19], inflammatory bowel disease [1], cardiac disease [7], liver cirrhosis and fibrosis [11] and breast cancer [31]. D. Upadhyay et al. / Review: Role of NMR metabonomics in Celiac DiseaseCeliac Disease (CeD) is a systemic autoimmune disease of small intestine that occurs as a consequence of intake of cereals like wheat, barley and rye in individuals who are genetically susceptible with human leukocyte antigen (HLA-DQ2 or HLA-DQ8) haplotypes [20]. Gluten protein and related prolamines present in these cereals have been identified as prominent factors that cause CeD. It affects around 0.7-3.0% of the population worldwide and its prevalence is increasing over the years as seen in United States and Europe [10,34,40]. CeD is characterised by both the presence of gluten-dependent gastrointestinal and extra gastrointestinal clinical manifestations of variable degree. These include diarrhoea, abdominal distension, failure to thrive and fatigue in infants and children, anemia, metabolic bone disease, liver diseases and ataxia and these complicate its diagnosis [35]. Currently screening of CeD is based on the detection of serological markers such as endomysial (EMA) and tissue transglutaminase (tTG) IgA antibodies, however, confirmation of diagnosis of CeD is achieved only after...

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Section: Intestinal Mucosamentioning

confidence: 88%

Section: Upadhyay Et Al / Review: Role Of Nmr Metabonomics In Celmentioning

confidence: 99%

Section: Bloodmentioning

confidence: 99%

Section: Intestinal Mucosamentioning

confidence: 99%

mentioning

confidence: 99%

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Role of NMR metabonomics in Celiac Disease (CeD)

Upadhyay

Sharma

Makharia

et al. 2017

BSI

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Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats

Gupta

Upadhayay

Sharma

et al. 2018

J of Neuroscience Research

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Oxidative stress and inflammation are implicated as cardinal mechanisms of neuronal death following stroke. In the present study citalopram (Cit) was investigated in a 2 h middle cerebral artery occlusion (MCAo) model of stroke in male Wistar rats. Pretreatment, posttreatment (Post Cit) and pre plus posttreatment (Pre + Post Cit) with Cit were evaluated for its neuroprotective effect. In pretreatment protocol, effect of Cit at three doses (2, 4, and 8 mg/kg) administered i.p., 1 h prior to MCAo was evaluated using neurological deficit score (NDS), motor deficit paradigms, and cerebral infarction 24 h post-MCAo. In posttreatment and pre plus posttreatment protocol, the effective dose of Cit (4 mg/kg) was administered i.p., 0.5 h post-reperfusion (Post Cit) only, and 1 h prior to MCAo and again at 0.5 h post-reperfusion (Pre + Post Cit), respectively. These two groups were assessed for NDS and cerebral infarction. Though NDS was significantly reduced in both Post Cit and Pre + Post Cit groups, significant reduction in cerebral infarction was evident only in Pre + Post Cit group. Infarct volume assessed by magnetic resonance imaging was significantly attenuated in Pre + Post Cit group (10.6 ± 1.1%) compared to MCAo control group (18.5 ± 3.0%). Further, Pre + Post Cit treatment significantly altered 17 metabolites along with attenuation of malondialdehyde, reduced glutathione, matrix metalloproteinases, and apoptotic markers as compared to MCAo control. These results support the neuroprotective effect of Cit, mediated through amelioration of oxidative stress, inflammation, apoptosis, and altered metabolic profile.

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Abnormalities in metabolic pathways in celiac disease investigated by the metabolic profiling of small intestinal mucosa, blood plasma and urine by NMR spectroscopy

et al. 2020

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Celiac disease (CeD) is an autoimmune enteropathy caused by gluten intake in genetically predisposed individuals. We investigated the metabolism of CeD by metabolic profiling of intestinal mucosa, blood plasma and urine using NMR spectroscopy and multivariate analysis. The metabolic profile of the small intestinal mucosa was compared between patients with CeD (n = 64) and disease controls (DCs, n = 30). The blood plasma and urinary metabolomes of CeD patients were compared with healthy controls (HCs, n = 39). Twelve metabolites (proline (Pro), arginine (Arg), glycine (Gly), histidine (His), glutamate (Glu), aspartate, tryptophan (Trp), fumarate, formate, succinate (Succ), glycerophosphocholine (GPC) and allantoin (Alln)) of intestinal mucosa differentiated CeD from controls. The metabolome of blood plasma with 18 metabolites (Pro, Arg, Gly, alanine, Glu, glutamine, glucose (Glc), lactate (Lac), acetate (Ace), acetoacetate (AcAc), β‐hydroxybutyrate (β‐OHB), pyruvate (Pyr), Succ, citrate (Cit), choline (Cho), creatine (Cr), phosphocreatine (PCr) and creatinine) and 9 metabolites of urine (Pro, Trp, β‐OHB, Pyr, Succ, N‐methylnicotinamide (NMN), aminohippurate (AHA), indoxyl sulfate (IS) and Alln) distinguished CeD from HCs. Our data demonstrated changes in nine metabolic pathways. The altered metabolites were associated with increased oxidative stress (Alln), impaired healing and repair mechanisms (Pro, Arg), compromised anti‐inflammatory and cytoprotective processes (Gly, His, NMN), altered energy metabolism (Glc, Lac, β‐OHB, Ace, AcAc, Pyr, Succ, Cit, Cho, Cr and PCr), impaired membrane metabolism (GPC and Cho) and intestinal dysbiosis (AHA and IS). An orthogonal partial least square discriminant analysis model provided clear differentiation between patients with CeD and controls in all three specimens. A classification model built by combining the distinguishing metabolites of blood plasma and urine samples gave an AUC of 0.99 with 97.7% sensitivity, 93.3% specificity and a predictive accuracy of 95.1%, which was higher than for the models built separately using small intestinal mucosa, blood plasma and urine. In conclusion, a panel of metabolic biomarkers in intestinal biopsies, plasma and urine samples has potential to differentiate CeD from controls and may complement traditional tests to improve the diagnosis of CeD.

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Metabolic abnormalities of gastrointestinal mucosa in celiac disease: An in vitro proton nuclear magnetic resonance spectroscopy study

Abstract: NMR spectroscopy with multivariate analysis of duodenal mucosal biopsies revealed a characteristic metabolic profile in CeD patients. The work provided an insight in determining biomarker/s for villous atrophy and diagnosis of CeD patients.

Cited by 18 publications

References 26 publications

Role of NMR metabonomics in Celiac Disease (CeD)

Role of NMR metabonomics in Celiac Disease (CeD)

Citalopram attenuated neurobehavioral, biochemical, and metabolic alterations in transient middle cerebral artery occlusion model of stroke in male Wistar rats

Abnormalities in metabolic pathways in celiac disease investigated by the metabolic profiling of small intestinal mucosa, blood plasma and urine by NMR spectroscopy

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