Untargeted Metabolomics Insights into Newborns with Congenital Zika Infection

Zika virus (ZIKV), an emerging virus belonging to the Flaviviridae family, causes severe neurological clinical complications and has been associated with Guillain-Barré syndrome, fetal abnormalities known collectively as congenital Zika syndrome, and microcephaly. Studies have shown that ZIKV infection can alter cellular metabolism, directly affecting neural development. Brain growth requires controlled cellular metabolism, which is essential for cell proliferation and maturation. However, little is known regarding the metabolic profile of ZIKV-infected newborns and possible associations related to microcephaly. Furthering the understanding surrounding underlying mechanisms is essential to developing personalized treatments for affected individuals. Thus, metabolomics, the study of the metabolites produced by or modified in an organism, constitutes a valuable approach in the study of complex diseases. Here, 26 serum samples from ZIKV-positive newborns with or without microcephaly, as well as controls, were analyzed using an untargeted metabolomics approach involving gas chromatography–mass spectrometry (GC-MS). Significant alterations in essential and non-essential amino acids, as well as carbohydrates (including aldohexoses, such as glucose or mannose) and their derivatives (urea and pyruvic acid), were observed in the metabolic profiles analyzed. Our results provide insight into relevant metabolic processes in patients with ZIKV and microcephaly.

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Muscle and Serum Metabolomics for Different Chicken Breeds under Commercial Conditions by GC–MS

Foods ◽

10.3390/foods10092174 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2174

Author(s):

Chengkeng Tan ◽

Jinap Selamat ◽

Nuzul Noorahya Jambari ◽

Rashidah Sukor ◽

Suganya Murugesu ◽

...

Keyword(s):

Principal Component ◽

Pectoralis Major ◽

Untargeted Metabolomics ◽

Gas Chromatography Mass Spectrometry ◽

Serum Samples ◽

Food Fraud ◽

Village Chicken ◽

Premium Price ◽

Chicken Breeds ◽

Serum Metabolomics

Globally, village chicken is popular and is known as a premium meat with a higher price. Food fraud can occur by selling other chicken breeds at a premium price in local markets. This study aimed to distinguish local village chicken from other chicken breeds available in the market, namely, colored broiler (Hubbard), broiler (Cobb), and spent laying hen (Dekalb) in pectoralis major and serum under commercial conditions using an untargeted metabolomics approach. Both pectoralis major and serum were analyzed using gas chromatography–mass spectrometry (GC–MS). The principal component analysis (PCA) results distinguished four different chicken breeds into three main groups for pectoralis major and serum. A total of 30 and 40 characteristic metabolites were identified for pectoralis major and serum, respectively. The four chicken breeds were characterized by the abundance of metabolites such as amino acids (L−glutamic acid, L−threonine, L−serine, L−leucine), organic acids (L−lactic acid, succinic acid, 3−hydroxybutyric acid), sugars (D−allose, D−glucose), sugar alcohols (myo−inositol), and fatty acids (linoleic acid). Our results suggest that an untargeted metabolomics approach using GC–MS and PCA could discriminate chicken breeds for pectoralis major and serum under commercial conditions. In this study, village chicken could only be distinguished from colored broiler (Hubbard) by serum samples.

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Untargeted Metabolomics Analysis of the Serum Metabolic Signature of Childhood Obesity

Nutrients ◽

10.3390/nu14010214 ◽

2022 ◽

Vol 14 (1) ◽

pp. 214

Author(s):

Lukasz Szczerbinski ◽

Gladys Wojciechowska ◽

Adam Olichwier ◽

Mark A. Taylor ◽

Urszula Puchta ◽

...

Keyword(s):

Mass Spectrometry ◽

Childhood Obesity ◽

Adult Population ◽

Normal Weight ◽

Untargeted Metabolomics ◽

Gas Chromatography Mass Spectrometry ◽

Serum Samples ◽

Metabolic Signature ◽

Metabolomic Profiling ◽

Altered Lipid

Obesity rates among children are growing rapidly worldwide, placing massive pressure on healthcare systems. Untargeted metabolomics can expand our understanding of the pathogenesis of obesity and elucidate mechanisms related to its symptoms. However, the metabolic signatures of obesity in children have not been thoroughly investigated. Herein, we explored metabolites associated with obesity development in childhood. Untargeted metabolomic profiling was performed on fasting serum samples from 27 obese Caucasian children and adolescents and 15 sex- and age-matched normal-weight children. Three metabolomic assays were combined and yielded 726 unique identified metabolites: gas chromatography–mass spectrometry (GC–MS), hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC–MS/MS), and lipidomics. Univariate and multivariate analyses showed clear discrimination between the untargeted metabolomes of obese and normal-weight children, with 162 significantly differentially expressed metabolites between groups. Children with obesity had higher concentrations of branch-chained amino acids and various lipid metabolites, including phosphatidylcholines, cholesteryl esters, triglycerides. Thus, an early manifestation of obesity pathogenesis and its metabolic consequences in the serum metabolome are correlated with altered lipid metabolism. Obesity metabolite patterns in the adult population were very similar to the metabolic signature of childhood obesity. Identified metabolites could be potential biomarkers and used to study obesity pathomechanisms.

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Different Blood Metabolomics Profiles in Infants Consuming a Meat- or Dairy-Based Complementary Diet

Nutrients ◽

10.3390/nu13020388 ◽

2021 ◽

Vol 13 (2) ◽

pp. 388

Author(s):

Minghua Tang ◽

Nicholas E. Weaver ◽

Lillian M. Berman ◽

Laura D. Brown ◽

Audrey E. Hendricks ◽

...

Keyword(s):

Amino Acids ◽

Dietary Intervention ◽

Principal Component ◽

Essential Amino Acids ◽

Infant Growth ◽

Serum Samples ◽

Z Scores ◽

Protein Rich ◽

Over Time ◽

Complementary Diet

Background: Research is limited in evaluating the mechanisms responsible for infant growth in response to different protein-rich foods; Methods: Targeted and untargeted metabolomics analysis were conducted on serum samples collected from an infant controlled-feeding trial that participants consumed a meat- vs. dairy-based complementary diet from 5 to 12 months of age, and followed up at 24 months. Results: Isoleucine, valine, phenylalanine increased and threonine decreased over time among all participants; Although none of the individual essential amino acids had a significant impact on changes in growth Z scores from 5 to 12 months, principal component heavily weighted by BCAAs (leucine, isoleucine, valine) and phenylalanine had a positive association with changes in length-for-age Z score from 5 to 12 months. Concentrations of acylcarnitine-C4, acylcarnitine-C5 and acylcarnitine-C5:1 significantly increased over time with the dietary intervention, but none of the acylcarnitines were associated with infant growth Z scores. Quantitative trimethylamine N-oxide increased in the meat group from 5 to 12 months; Conclusions: Our findings suggest that increasing total protein intake by providing protein-rich complementary foods was associated with increased concentrations of certain essential amino acids and short-chain acyl-carnitines. The sources of protein-rich foods (e.g., meat vs. dairy) did not appear to differentially impact serum metabolites, and comprehensive mechanistic investigations are needed to identify other contributors or mediators of the diet-induced infant growth trajectories.

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Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽

10.3390/metabo11080482 ◽

2021 ◽

Vol 11 (8) ◽

pp. 482

Author(s):

Jae-Kwon Jo ◽

Seung-Ho Seo ◽

Seong-Eun Park ◽

Hyun-Woo Kim ◽

Eun-Ju Kim ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

High Fat Diet ◽

Amplicon Sequencing ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Rrna Gene ◽

High Fat ◽

Underlying Mechanisms ◽

Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

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Sirt5 deficiency causes post-translational protein malonylation and dysregulated cellular metabolism in chondrocytes under obesity conditions

10.1101/2020.11.30.404103 ◽

2020 ◽

Author(s):

Shouan Zhu ◽

Albert Batushansky ◽

Anita Jopkiewicz ◽

Dawid Makosa ◽

Kenneth M. Humphries ◽

...

Keyword(s):

Cellular Metabolism ◽

Tca Cycle ◽

Gas Chromatography Mass Spectrometry ◽

Dependent Manner ◽

Joint Injury ◽

Primary Chondrocytes ◽

Wide Range ◽

Chondrocyte Metabolism ◽

High Concentrations

ABSTRACTObjectiveObesity accelerates the development of osteoarthritis (OA) during aging and is associated with altered chondrocyte cellular metabolism. The objective of this study was to investigate the role of sirtuin 5 (SIRT5) in regulating chondrocyte protein lysine malonylation (MaK) and cellular metabolism under obesity-related conditions.MethodsMaK and SIRT5 were immunostained in knee articular cartilage of obese db/db mice and different aged C57BL6 mice with or without destabilization of the medial meniscus (DMM) surgery to induce OA. Primary chondrocytes were isolated from 7-day-old WT and Sirt5−/− mice and treated with varying concentrations of glucose and insulin to mimic obesity. Sirt5-dependent effects on MaK and metabolism were evaluated by Western blot, Seahorse Respirometry, and gas/chromatography-mass/spectrometry (GC-MS) metabolic profiling.ResultsMaK was significantly increased in cartilage of db/db mice and in chondrocytes treated with high concentrations of glucose and insulin (GluhiInshi). Sirt5 protein was increased in an age-dependent manner following joint injury, and Sirt5 deficient primary chondrocytes had increased MaK, decreased glycolysis rate, and reduced basal mitochondrial respiration. GC-MS identified 41 metabolites. Sirt5 deficiency altered 13 distinct metabolites under basal conditions and 18 metabolites under GluhiInshi treatment. Pathway analysis identified a wide range of Sirt5-dependent altered metabolic pathways that include amino acid metabolism, TCA cycle, and glycolysis.ConclusionThis study provides the first evidence that Sirt5 broadly regulates chondrocyte metabolism. We observed changes in Sirt5 and MaK levels in cartilage with obesity and joint injury, suggesting that the Sirt5-MaK pathway may contribute to altered chondrocyte metabolism that occurs during OA development.

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Measuring swainsonine in serum of cancer patients: phase I clinical trial

Clinical Chemistry ◽

10.1093/clinchem/40.3.426 ◽

1994 ◽

Vol 40 (3) ◽

pp. 426-430 ◽

Cited By ~ 15

Author(s):

J A Baptista ◽

P Goss ◽

M Nghiem ◽

J J Krepinsky ◽

M Baker ◽

...

Keyword(s):

Clinical Trial ◽

Phase I ◽

Cancer Patients ◽

Biological Fluids ◽

Competitive Inhibitor ◽

Phase I Clinical Trial ◽

Gas Chromatography Mass Spectrometry ◽

Gas Liquid Chromatography ◽

Serum Samples ◽

Internal Standards

Abstract Swainsonine, an indolizidine alkaloid and competitive inhibitor of Golgi alpha-mannosidase II (EC 3.2.1.114), reduces tumor growth and stimulates immune function in mice. On the basis of these observations, a phase I clinical trial was initiated to determine whether swainsonine could be administered safely to cancer patients. We describe a method for extraction, acetylation, and quantification of swainsonine in human serum samples. Methyl alpha-D-mannopyranoside and methyl beta-D-galactopyranoside were added to serum samples as internal standards and, after sequential extraction of lipids and proteins with chloroform and acetonitrile, respectively, samples were acetylated with acetic anhydride and 4-dimethylaminopyridine and separated by gas-liquid chromatography. The identity of swainsonine and the internal standards after their extraction from serum and acetylation was confirmed by gas chromatography/mass spectrometry. Swainsonine was recovered at an efficiency of 90%, relative to internal standards, and calibration graphs were rectilinear from 3 to 18 mg/L with a detection limit of approximately 0.1 mg/L. The CV for multiple samples was < or = 6.7%. In patients receiving swainsonine (50-550 micrograms/kg per day) continuously for 5 days by intravenous infusion, serum concentrations of the drug reached 3-11.8 mg/L, 100 to 400 times greater than the 50% inhibitory concentration for Golgi alpha-mannosidase II and lysosomal alpha-mannosidases. Accurate measurements of swainsonine in biological fluids with this method should facilitate further clinical studies with the drug.

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Metabolomics Fingerprint Induced by the Intranigral Inoculation of Exogenous Human Alpha-Synuclein Oligomers in a Rat Model of Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21186745 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6745

Author(s):

Federica Murgia ◽

Luigi Atzori ◽

Ezio Carboni ◽

Maria Laura Santoru ◽

Aran Hendren ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dehydroascorbic Acid ◽

Alpha Synuclein ◽

Mass Spectrometry Analysis ◽

Substantia Nigra Pars Compacta ◽

Gas Chromatography Mass Spectrometry ◽

Serum Samples ◽

Spectrometry Analysis ◽

Metabolite Content

Parkinson’s disease (PD) is considered a synucleinopathy because of the intraneuronal accumulation of aggregated α-synuclein (αSyn). Recent evidence points to soluble αSyn-oligomers (αSynO) as the main cytotoxic species responsible for cell death. Given the pivotal role of αSyn in PD, αSyn-based models are crucial for the investigation of toxic mechanisms and the identification of new therapeutic targets in PD. By using a metabolomics approach, we evaluated the metabolic profile of brain and serum samples of rats infused unilaterally with preformed human αSynOs (HαSynOs), or vehicle, into the substantia nigra pars compacta (SNpc). Three months postinfusion, the striatum was dissected for striatal dopamine (DA) measurements via High Pressure Liquid Chromatography (HPLC) analysis and mesencephalon and serum samples were collected for the evaluation of metabolite content via gas chromatography mass spectrometry analysis. Multivariate, univariate and correlation statistics were applied. A 40% decrease of DA content was measured in the HαSynO-infused striatum as compared to the contralateral and the vehicle-infused striata. Decreased levels of dehydroascorbic acid, myo-inositol, and glycine, and increased levels of threonine, were found in the mesencephalon, while increased contents of fructose and mannose, and a decrease in glycine and urea, were found in the serum of HαSynO-infused rats. The significant correlation between DA and metabolite content indicated that metabolic variations reflected the nigrostriatal degeneration. Collectively, the metabolomic fingerprint of HαSynO-infused rats points to an increase of oxidative stress markers, in line with PD neuropathology, and provides hints for potential biomarkers of PD.

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Metabolite Markers for Characterizing Sasang Constitution Type through GC-MS and 1H NMR-Based Metabolomics Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/8783496 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Eun-Ju Kim ◽

Young-Shick Hong ◽

Seung-Ho Seo ◽

Seong-Eun Park ◽

Chang-Su Na ◽

...

Keyword(s):

Fatty Acids ◽

Serum Lactate ◽

Normal Weight ◽

Gas Chromatography Mass Spectrometry ◽

Human Beings ◽

Serum Samples ◽

Sasang Constitution ◽

Metabolomics Study ◽

Constitution Type ◽

Lactate Levels

Sasang constitutional medicine classifies human beings into four types based on their physical and psychological characteristics. Despite its potential value in achieving personalized medicine, the diagnosis of sasang constitution (SC) type is complex and subjective. In this study, gas chromatography–mass spectrometry and 1H nuclear magnetic resonance–based metabolic analyses were conducted to find maker metabolites in serum and urine according to different SC types. Although some samples were overlapped on orthogonal projection to latent structure discriminant analysis score plots, serum samples showed separation between different SC types. Levels of lactate, glutamate, triglyceride, and fatty acids in serum and glycolic acid in urine of Tae-Eum type were higher than those of So-Eum and So-Yang type. Fatty acids, triglyceride, and lactate levels were found to be metabolites related to body mass index, indicating that marker metabolites for the diagnosis of SC type could be associated with obese. However, Tae-Eum type showed higher lactate levels in serum than So-Yang type for both normal weight and overweight groups, suggesting that the contents of serum lactate might be dependent on the SC type regardless of body weight. These results suggest that metabolomics analysis could be used to determine SC type.

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Determination of Mammalian Lignans in Biological Samples by Modified Gas Chromatography/Mass Spectrometry

Journal of AOAC International ◽

10.1093/jaoac/90.3.641 ◽

2007 ◽

Vol 90 (3) ◽

pp. 641-646 ◽

Cited By ~ 5

Author(s):

Ajay Bommareddy ◽

Bhanu L Arasada ◽

Duane P Mathees ◽

Chandradhar Dwivedi

Keyword(s):

Mass Spectrometry ◽

Gas Chromatography ◽

Gas Chromatography Mass Spectrometry ◽

Serum Samples ◽

Selected Ion Monitoring ◽

Beneficial Effects ◽

Chromatography Mass Spectrometry ◽

Flaxseed Meal

Abstract Lignans in flaxseed have been part of the human diet for centuries. In 1955, the isolation and structure of the lignan derivative secoisolariciresinol diglucoside (SDG) was reported. The biological role of SDG and mammalian lignan metabolites enterodiol and enterolactone was initially reported 20 years later. Experimental evidences showed the beneficial effects of lignans on breast, colon, and thyroid cancer. A modified gas chromatography/mass spectrometry (GC/MS) assay was developed for lignans in serum and colon samples of rats fed flaxseed meal. The method developed for the analysis of metabolites involves extraction and derivatization of samples and quantitative analysis by selected ion monitoring using GC/MS. The levels of lignan metabolites enterodiol and enterolactone were determined to be 0.013 and 0.23 M in serum samples and 0.008 and 1.63 M in colon samples.

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Monitoring drug concentrations in a case of combined overdosage with primidone and methsuximide.

Clinical Chemistry ◽

10.1093/clinchem/22.6.915 ◽

1976 ◽

Vol 22 (6) ◽

pp. 915-921 ◽

Cited By ~ 6

Author(s):

G F Johnson ◽

C J Least ◽

J W Serum ◽

E B Solow ◽

H M Solomon

Keyword(s):

Mass Spectrometry ◽

Gas Chromatography ◽

Liquid Chromatography ◽

Gas Chromatography Mass Spectrometry ◽

Gas Liquid Chromatography ◽

Therapeutic Decision ◽

Serum Samples ◽

Monitoring Drug ◽

Drug Concentrations

Abstract We describe a case of fatal overdosage with primidone and methsuximide. During the early phase of the patient's hospital course we found concentrations of methsuximide, N-desmethylmethsuximide, and primidone in serum that far exceeded the usual therapeutic concentrations, as determined by gas-liquid chromatography. Determination of N-desmethylmethsuximide in peritoneal fluid demonstrated concentrations comparable to those in serum. This led to the therapeutic decision to manage the patient by dialysis. Subsequently, serum samples collected during the course of hospitalization were analyzed quantitatively by gas-liquid chromatography for methsuximide, N-desmethylmethsuximide, primidone, phenobarbital, and diphenylhydantoin. Selected serum specimens were also analyzed by gas chromatography-mass spectrometry, and N-methyl-2-hydroxymethyl-2-phenylsuccinimide, a metabolite of methsuximide not previously described in human serum, was identified by analysis of its mass spectrum.

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