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Metabolomics in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 58194

Special Issue Editors

Dr. Óscar J. Pozo

E-Mail Website
Guest Editor
Integrative Pharmacology and Systems Neuroscience Research Group, IMIM-Hospital del Mar Medical Research Institute, Dr. Aiguader 88, 08003 Barcelona, Spain
Interests: analytical chemistry; mass spectrometry; chromatography; steroids; metabolomics; metabolism; bioanalysis
Dr. Ana Varela Coelho

E-Mail Website
Guest Editor
Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), Oeiras, Portugal
Interests: proteomics; metabolomics; mass spectrometry; host-pathogen interaction; tissue/organ regeneration; marine organisms; antimicrobials; echinoderms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolomics is the systematic quantification of a large part of the metabolites of a biological system (cell, tissue, organ, biological fluid, or organism) at a specific point in time. Based on the goal of the determination, metabolomics might be divided into untargeted (aiming to determine the largest part of the metabolome) or targeted (focused on the specific quantification of a selected part of the metabolome).

Mass spectrometry and nuclear magnetic resonance spectroscopy are the gold standard techniques for metabolomics. In the particular case of mass spectrometry, we can find a wealth of instrumental configurations. In addition, alternative techniques—either standalone or in combination with mass spectrometry—have also been tested for metabolomic studies. Notable examples are ion mobility spectrometry, Raman spectroscopy, infrared spectroscopy, and others.

Since metabolomics analysis generates large-scale and complex datasets, data analysis is crucial to extract biologically relevant information. Many metabolomics studies feature moderate sample counts, extremely high dimensional datasets, and complex experimental designs that require careful use of advanced statistics and machine learning.

Metabolomics is considered to provide a close link to the organism’s phenotype. Thus, alterations in the metabolome can be used as biomarkers for diagnosis, prognosis, or evolution monitoring of a wide range of diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, or rare diseases. Additionally, metabolomics can provide useful information regarding the mechanism underlying the pathological status. For all these reasons, metabolomics have become one of the most promising tools in health and disease.

This Special Issue, “Metabolomics in Health and Disease”, aims to provide a summary of the field and to explore the application of metabolomics for diagnosis, prognosis, and/or mechanism elucidation in different diseases using either human samples or animal models for disease. We warmly welcome original research and review articles dealing with these aspects.

Dr. Óscar J. Pozo
Dr. Ana Varela Coelho
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomarkers
  • mass spectrometry
  • NMR
  • alternative analytical platforms for metabolomics
  • data processing workflows
  • computational biomarker discovery
  • volatile metabolomics
  • cancer
  • neurodegenerative diseases
  • cardiovascular diseases
  • epidemiology
  • rare diseases

Published Papers (20 papers)

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17 pages, 3784 KiB  
Article
Mass Spectrometry-Based Proteomic and Metabolomic Profiling of Serum Samples for Discovery and Validation of Tuberculosis Diagnostic Biomarker Signature
by Ana Filipa Fernandes, Luís Gafeira Gonçalves, Maria Bento, Sandra I. Anjo, Bruno Manadas, Clara Barroso, Miguel Villar, Rita Macedo, Maria João Simões and Ana Varela Coelho
Int. J. Mol. Sci. 2022, 23(22), 13733; https://doi.org/10.3390/ijms232213733 - 08 Nov 2022
Cited by 2 | Viewed by 2011
Abstract
Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. [...] Read more.
Tuberculosis (TB) is a transmissible disease listed as one of the 10 leading causes of death worldwide (10 million infected in 2019). A swift and precise diagnosis is essential to forestall its transmission, for which the discovery of effective diagnostic biomarkers is crucial. In this study, we aimed to discover molecular biomarkers for the early diagnosis of tuberculosis. Two independent cohorts comprising 29 and 34 subjects were assayed by proteomics, and 49 were included for metabolomic analysis. All subjects were arranged into three experimental groups—healthy controls (controls), latent TB infection (LTBI), and TB patients. LC-MS/MS blood serum protein and metabolite levels were submitted to univariate, multivariate, and ROC analysis. From the 149 proteins quantified in the discovery set, 25 were found to be differentially abundant between controls and TB patients. The AUC, specificity, and sensitivity, determined by ROC statistical analysis of the model composed of four of these proteins considering both proteomic sets, were 0.96, 93%, and 91%, respectively. The five metabolites (9-methyluric acid, indole-3-lactic acid, trans-3-indoleacrylic acid, hexanoylglycine, and N-acetyl-L-leucine) that better discriminate the control and TB patient groups (VIP > 1.75) from a total of 92 metabolites quantified in both ionization modes were submitted to ROC analysis. An AUC = 1 was determined, with all samples being correctly assigned to the respective experimental group. An integrated ROC analysis enrolling one protein and four metabolites was also performed for the common control and TB patients in the proteomic and metabolomic groups. This combined signature correctly assigned the 12 controls and 12 patients used only for prediction (AUC = 1, specificity = 100%, and sensitivity = 100%). This multiomics approach revealed a biomarker signature for tuberculosis diagnosis that could be potentially used for developing a point-of-care diagnosis clinical test. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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18 pages, 4665 KiB  
Article
A Novel Approach of SWATH-Based Metabolomics Analysis Using the Human Metabolome Database Spectral Library
by Hassan Shikshaky, Eman Abdelnaby Ahmed, Ali Mostafa Anwar, Aya Osama, Shahd Ezzeldin, Antony Nasr, Sebaey Mahgoub and Sameh Magdeldin
Int. J. Mol. Sci. 2022, 23(18), 10908; https://doi.org/10.3390/ijms231810908 - 18 Sep 2022
Cited by 2 | Viewed by 2110
Abstract
Metabolomics is a potential approach to paving new avenues for clinical diagnosis, molecular medicine, and therapeutic drug monitoring and development. The conventional metabolomics analysis pipeline depends on the data-independent acquisition (DIA) technique. Although powerful, it still suffers from stochastic, non-reproducible ion selection across [...] Read more.
Metabolomics is a potential approach to paving new avenues for clinical diagnosis, molecular medicine, and therapeutic drug monitoring and development. The conventional metabolomics analysis pipeline depends on the data-independent acquisition (DIA) technique. Although powerful, it still suffers from stochastic, non-reproducible ion selection across samples. Despite the presence of different metabolomics workbenches, metabolite identification remains a tedious and time-consuming task. Consequently, sequential windowed acquisition of all theoretical MS (SWATH) acquisition has attracted much attention to overcome this limitation. This article aims to develop a novel SWATH platform for data analysis with a generation of an accurate mass spectral library for metabolite identification using SWATH acquisition. The workflow was validated using inclusion/exclusion compound lists. The false-positive identification was 3.4% from the non-endogenous drugs with 96.6% specificity. The workflow has proven to overcome background noise despite the complexity of the SWATH sample. From the Human Metabolome Database (HMDB), 1282 compounds were tested in various biological samples to demonstrate the feasibility of the workflow. The current study identified 377 compounds in positive and 303 in negative modes with 392 unique non-redundant metabolites. Finally, a free software tool, SASA, was developed to analyze SWATH-acquired samples using the proposed pipeline. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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17 pages, 1930 KiB  
Article
Urine Metabolomic Profile of Breast- versus Formula-Fed Neonates Using a Synbiotic-Enriched Formula
by Vasiliki Falaina, Charalambos Fotakis, Theodora Boutsikou, Thalia Tsiaka, Georgios Moros, Sotirios Ouzounis, Vasiliki Andreou, Zoi Iliodromiti, Theodoros Xanthos, Yvan Vandenplas, Nicoletta Iacovidou and Panagiotis Zoumpoulakis
Int. J. Mol. Sci. 2022, 23(18), 10476; https://doi.org/10.3390/ijms231810476 - 09 Sep 2022
Cited by 1 | Viewed by 1586
Abstract
The aim of this study was to compare the urine metabolic fingerprint of healthy neonates exclusively breastfed with that of neonates fed with a synbiotic-enriched formula (Rontamil® Complete 1) at four time points (the 3rd and 15th days of life and the [...] Read more.
The aim of this study was to compare the urine metabolic fingerprint of healthy neonates exclusively breastfed with that of neonates fed with a synbiotic-enriched formula (Rontamil® Complete 1) at four time points (the 3rd and 15th days of life and the 2nd and 3rd months). The determination of urine metabolic fingerprint was performed using NMR metabolomics. Multivariate data analyses were performed with SIMCA-P 15.0 software and R language. Non-distinct profiles for both groups (breastfeeding and synbiotic formula) for the two first time points (3rd and 15th days of life) were detected, whereas after the 2nd month of life, a discrimination trend was observed between the two groups, which was further confirmed at the 3rd month of life. A clear discrimination of the synbiotic formula samples was evident when comparing the metabolites taken in the first days of life (3rd day) with those taken in the 2nd and 3rd months of life. In both cases, OPLS-DA models explained more than 75% of the metabolic variance. Non-distinct metabolomic profiles were obtained between breastfed and synbiotic-formula-fed neonates up to the 15th day of life. Discrimination trends were observed only after the 2nd month of the study, which could be attributed to breastfeeding variations and the consequent dynamic profile of urine metabolites compared to the stable ingredients of the synbiotic formula. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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18 pages, 5433 KiB  
Article
Metabolomic Profiling of End-Stage Heart Failure Secondary to Chronic Chagas Cardiomyopathy
by Martha Lucía Díaz, Karl Burgess, Richard Burchmore, María Adelaida Gómez, Sergio Alejandro Gómez-Ochoa, Luis Eduardo Echeverría, Carlos Morillo and Clara Isabel González
Int. J. Mol. Sci. 2022, 23(18), 10456; https://doi.org/10.3390/ijms231810456 - 09 Sep 2022
Cited by 5 | Viewed by 1916
Abstract
Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe clinical form of chronic Chagas disease, representing one of the leading causes of morbidity and mortality in Latin America, and a growing global public health problem. There is currently no approved treatment for [...] Read more.
Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe clinical form of chronic Chagas disease, representing one of the leading causes of morbidity and mortality in Latin America, and a growing global public health problem. There is currently no approved treatment for CCC; however, omics technologies have enabled significant progress to be made in the search for new therapeutic targets. The metabolic alterations associated with pathogenic mechanisms of CCC and their relationship to cellular and immunopathogenic processes in cardiac tissue remain largely unknown. This exploratory study aimed to evaluate the potential underlying pathogenic mechanisms in the failing myocardium of patients with end-stage heart failure (ESHF) secondary to CCC by applying an untargeted metabolomic profiling approach. Cardiac tissue samples from the left ventricle of patients with ESHF of CCC etiology (n = 7) and healthy donors (n = 7) were analyzed using liquid chromatography-mass spectrometry. Metabolite profiles showed altered branched-chain amino acid and acylcarnitine levels, decreased fatty acid uptake and oxidation, increased activity of the pentose phosphate pathway, dysregulation of the TCA cycle, and alterations in critical cellular antioxidant systems. These findings suggest processes of energy deficit, alterations in substrate availability, and enhanced production of reactive oxygen species in the affected myocardium. This profile potentially contributes to the development and maintenance of a chronic inflammatory state that leads to progression and severity of CCC. Further studies involving larger sample sizes and comparisons with heart failure patients without CCC are needed to validate these results, opening an avenue to investigate new therapeutic approaches for the treatment and prevention of progression of this unique and severe cardiomyopathy. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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23 pages, 3292 KiB  
Article
Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
by Xiaoyu Che, Christopher R. Brydges, Yuanzhi Yu, Adam Price, Shreyas Joshi, Ayan Roy, Bohyun Lee, Dinesh K. Barupal, Aaron Cheng, Dana March Palmer, Susan Levine, Daniel L. Peterson, Suzanne D. Vernon, Lucinda Bateman, Mady Hornig, Jose G. Montoya, Anthony L. Komaroff, Oliver Fiehn and W. Ian Lipkin
Int. J. Mol. Sci. 2022, 23(14), 7906; https://doi.org/10.3390/ijms23147906 - 18 Jul 2022
Cited by 12 | Viewed by 8398
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, [...] Read more.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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24 pages, 7186 KiB  
Article
Serum Metabolomics Reveals Distinct Profiles during Ischemia and Reperfusion in a Porcine Model of Myocardial Ischemia–Reperfusion
by Eric Goetzman, Zhenwei Gong, Dhivyaa Rajasundaram, Ishan Muzumdar, Traci Goodchild, David Lefer and Radhika Muzumdar
Int. J. Mol. Sci. 2022, 23(12), 6711; https://doi.org/10.3390/ijms23126711 - 16 Jun 2022
Cited by 4 | Viewed by 2255
Abstract
Acute myocardial infarction (MI) is one of the leading causes of death worldwide. Early identification of ischemia and establishing reperfusion remain cornerstones in the treatment of MI, as mortality and morbidity can be significantly reduced by establishing reperfusion to the affected areas. The [...] Read more.
Acute myocardial infarction (MI) is one of the leading causes of death worldwide. Early identification of ischemia and establishing reperfusion remain cornerstones in the treatment of MI, as mortality and morbidity can be significantly reduced by establishing reperfusion to the affected areas. The aim of the current study was to investigate the metabolomic changes in the serum in a swine model of MI induced by ischemia and reperfusion (I/R) injury, and to identify circulating metabolomic biomarkers for myocardial injury at different phases. Female Yucatan minipigs were subjected to 60 min of ischemia followed by reperfusion, and serum samples were collected at baseline, 60 min of ischemia, 4 h of reperfusion, and 24 h of reperfusion. Circulating metabolites were analyzed using an untargeted metabolomic approach. A bioinformatic approach revealed that serum metabolites show distinct profiles during ischemia and during early and late reperfusion. Some notable changes during ischemia include accumulation of metabolites that indicate impaired mitochondrial function and N-terminally modified amino acids. Changes in branched-chain amino-acid metabolites were noted during early reperfusion, while bile acid pathway derivatives and intermediates predominated in the late reperfusion phases. This indicates a potential for such an approach toward identification of the distinct phases of ischemia and reperfusion in clinical situations. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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21 pages, 3296 KiB  
Article
Metabolomic Profiling of Angiotensin-II-Induced Abdominal Aortic Aneurysm in Ldlr−/− Mice Points to Alteration of Nitric Oxide, Lipid, and Energy Metabolisms
by Juan Manuel Chao de la Barca, Alexis Richard, Pauline Robert, Maroua Eid, Olivier Fouquet, Lydie Tessier, Céline Wetterwald, Justine Faure, Celine Fassot, Daniel Henrion, Pascal Reynier and Laurent Loufrani
Int. J. Mol. Sci. 2022, 23(12), 6387; https://doi.org/10.3390/ijms23126387 - 07 Jun 2022
Cited by 6 | Viewed by 2591
Abstract
Aneurysm is the second-most common disease affecting the aorta worldwide after atherosclerosis. While several clinical metabolomic studies have been reported, no study has reported deep metabolomic phenotyping in experimental animal models of aortic aneurysm. We performed a targeted metabolomics study on the blood [...] Read more.
Aneurysm is the second-most common disease affecting the aorta worldwide after atherosclerosis. While several clinical metabolomic studies have been reported, no study has reported deep metabolomic phenotyping in experimental animal models of aortic aneurysm. We performed a targeted metabolomics study on the blood and aortas of an experimental mice model of aortic aneurysm generated by high-cholesterol diet and angiotensin II in Ldlr−/− mice. The mice model showed a significant increase in media/lumen ratio and wall area, which is associated with lipid deposition within the adventitia, describing a hypertrophic remodeling with an aneurysm profile of the abdominal aorta. Altered aortas showed increased collagen remodeling, disruption of lipid metabolism, decreased glucose, nitric oxide and lysine metabolisms, and increased polyamines and asymmetric dimethylarginine (ADMA) production. In blood, a major hyperlipidemia was observed with decreased concentrations of glutamine, glycine, taurine, and carnitine, and increased concentrations of the branched amino acids (BCAA). The BCAA/glycine and BCAA/glutamine ratios discriminated with very good sensitivity and specificity between aneurysmatic and non-aneurysmatic mice. To conclude, our results reveal that experimental induction of aortic aneurysms causes a profound alteration in the metabolic profile in aortas and blood, mainly centered on an alteration of NO, lipid, and energetic metabolisms. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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19 pages, 1924 KiB  
Article
Metabolomic Analysis of Serum and Tear Samples from Patients with Obesity and Type 2 Diabetes Mellitus
by Erdenetsetseg Nokhoijav, Andrea Guba, Ajneesh Kumar, Balázs Kunkli, Gergő Kalló, Miklós Káplár, Sándor Somodi, Ildikó Garai, Adrienne Csutak, Noémi Tóth, Miklós Emri, József Tőzsér and Éva Csősz
Int. J. Mol. Sci. 2022, 23(9), 4534; https://doi.org/10.3390/ijms23094534 - 20 Apr 2022
Cited by 9 | Viewed by 2598
Abstract
Metabolomics strategies are widely used to examine obesity and type 2 diabetes (T2D). Patients with obesity (n = 31) or T2D (n = 26) and sex- and age-matched controls (n = 28) were recruited, and serum and tear samples were [...] Read more.
Metabolomics strategies are widely used to examine obesity and type 2 diabetes (T2D). Patients with obesity (n = 31) or T2D (n = 26) and sex- and age-matched controls (n = 28) were recruited, and serum and tear samples were collected. The concentration of 23 amino acids and 10 biogenic amines in serum and tear samples was analyzed. Statistical analysis and Pearson correlation analysis along with network analysis were carried out. Compared to controls, changes in the level of 6 analytes in the obese group and of 10 analytes in the T2D group were statistically significant. For obesity, the energy generation, while for T2D, the involvement of NO synthesis and its relation to insulin signaling and inflammation, were characteristic. We found that BCAA and glutamine metabolism, urea cycle, and beta-oxidation make up crucial parts of the metabolic changes in T2D. According to our data, the retromer-mediated retrograde transport, the ethanolamine metabolism, and, consequently, the endocannabinoid signaling and phospholipid metabolism were characteristic of both conditions and can be relevant pathways to understanding and treating insulin resistance. By providing potential therapeutic targets and new starting points for mechanistic studies, our results emphasize the importance of complex data analysis procedures to better understand the pathomechanism of obesity and diabetes. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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17 pages, 2483 KiB  
Article
Uncontrolled Thyroid during Pregnancy Alters the Circulative and Exerted Metabolome
by Charalambos Fotakis, Giorgos Moros, Anna Kontogeorgou, Nicoletta Iacovidou, Theodora Boutsikou and Panagiotis Zoumpoulakis
Int. J. Mol. Sci. 2022, 23(8), 4248; https://doi.org/10.3390/ijms23084248 - 12 Apr 2022
Cited by 3 | Viewed by 1958
Abstract
Normal levels of thyroid hormones (THs) are essential for a normal pregnancy outcome, fetal growth and the normal function of the central nervous system. Hypothyroidism, a common endocrine disorder during pregnancy, is a significant metabolic factor leading to cognitive impairments. It is essential [...] Read more.
Normal levels of thyroid hormones (THs) are essential for a normal pregnancy outcome, fetal growth and the normal function of the central nervous system. Hypothyroidism, a common endocrine disorder during pregnancy, is a significant metabolic factor leading to cognitive impairments. It is essential to investigate whether patients with thyroid dysfunction may present an altered circulative and excreted metabolic profile, even after receiving treatment with thyroxine supplements. NMR metabolomics was employed to analyze 90 serum and corresponding colostrum samples. Parallel analyses of the two biological specimens provided a snapshot of the maternal metabolism through the excretive and circulating characteristics of mothers. The metabolomics data were analyzed by performing multivariate statistical, biomarker and pathway analyses. Our results highlight the impact of hypothyroidism on metabolites’ composition during pregnancy and lactation. Thyroid disorder causing metabolite fluctuations may lead to impaired lipid and glucose metabolic pathways as well as aberrant prenatal neurodevelopment, thus posing a background for the occurrence of metabolic syndrome or neurogenerative diseases later in life. This risk applies to not only untreated but also hypothyroid women under replacement therapy since our findings in both biofluids framed a different metabolic phenotype for the latter group, thus emphasizing the need to monitor women adequately after treatment initiation. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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20 pages, 1460 KiB  
Article
The Metabolic Impact of Two Different Parenteral Nutrition Lipid Emulsions in Children after Hematopoietic Stem Cell Transplantation: A Lipidomics Investigation
by Oscar Daniel Rangel-Huerta, María José de la Torre-Aguilar, María Dolores Mesa, Katherine Flores-Rojas, Juan Luis Pérez-Navero, María Auxiliadora Baena-Gómez, Angel Gil and Mercedes Gil-Campos
Int. J. Mol. Sci. 2022, 23(7), 3667; https://doi.org/10.3390/ijms23073667 - 27 Mar 2022
Cited by 3 | Viewed by 2421
Abstract
Hematopoietic stem cell transplantation (HSCT) involves the infusion of either bone marrow or blood cells preceded by toxic chemotherapy. However, there is little knowledge about the clinical benefits of parenteral nutrition (PN) in patients receiving high-dose chemotherapy during HSCT. We investigated the lipidomic [...] Read more.
Hematopoietic stem cell transplantation (HSCT) involves the infusion of either bone marrow or blood cells preceded by toxic chemotherapy. However, there is little knowledge about the clinical benefits of parenteral nutrition (PN) in patients receiving high-dose chemotherapy during HSCT. We investigated the lipidomic profile of plasma and the targeted fatty acid profiles of plasma and erythrocytes in children after HSCT using PN with either a fish oil-based lipid emulsion or a classic soybean oil emulsion. An untargeted liquid chromatography high-resolution mass spectrometry platform connected with a novel in silico annotation algorithm was utilized to determine the most relevant chemical subclasses affected. In addition, we explored the interrelation between the lipidomics profile in plasma, the targeted fatty acid profile in plasma and erythrocytes, several biomarkers of inflammation, and antioxidant defense using an innovative data integration analysis based on Latent Components. We observed that the fish oil-based lipid emulsion had an impact in several lipid subclasses, mainly glycerophosphocholines (PC), glycerophosphoserines (PS), glycerophosphoethanolamines (PE), oxidized PE (O-PE), 1-alkyl,2-acyl PS, lysophosphatidylethanolamines (LPE), oxidized PS (O-PS) and dicarboxylic acids. In contrast, the classic soybean oil emulsion did not. Several connections across the different blocks of data were found and aid in interpreting the impact of the lipid emulsions on metabolic health. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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14 pages, 1576 KiB  
Article
Evaluation of Metabolic Changes in Acute Intermittent Porphyria Patients by Targeted Metabolomics
by Alex Gomez-Gomez, Paula Aguilera, Klaus Langohr, Gregori Casals, Cristina Pavon, Josep Marcos, Jordi To-Figueras and Oscar J. Pozo
Int. J. Mol. Sci. 2022, 23(6), 3219; https://doi.org/10.3390/ijms23063219 - 16 Mar 2022
Cited by 7 | Viewed by 2482
Abstract
Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities [...] Read more.
Acute intermittent porphyria (AIP) is an inherited rare hepatic disorder due to mutations within the hydroxymethylbilane gene. AIP patients with active disease overproduce aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver which are exported inducing severe neurological attacks. Different hepatic metabolic abnormalities have been described to be associated with this condition. The goal of this research was to explore the metabolome of symptomatic AIP patients by state-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS). A case versus control study including 18 symptomatic AIP patients and 33 healthy controls was performed. Plasmatic levels of 51 metabolites and 16 ratios belonging to four metabolic pathways were determined. The results showed that the AIP patients presented significant changes in the two main areas of the metabolome under study: (a) the tryptophan/kynurenine pathway with an increase of tryptophan in plasma together with increase of the kynurenine/tryptophan ratio; and (b) changes in the tricarboxylic acid cycle (TCA) including increase of succinic acid and decrease of the fumaric acid/succinic acid ratio. We performed a complementary in vitro study adding ALA to hepatocytes media that showed some of the effects on the TCA cycle were parallel to those observed in vivo. Our study confirms in plasma previous results obtained in urine showing that AIP patients present a moderate increase of the kynurenine/tryptophan ratio possibly associated with inflammation. In addition, it also reports changes in the mitochondrial TCA cycle that, despite requiring further research, could be associated with an energy misbalance due to sustained overproduction of heme-precursors in the liver. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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18 pages, 2986 KiB  
Article
Comprehensive Targeted Metabolomic Study in the Lung, Plasma, and Urine of PPE/LPS-Induced COPD Mice Model
by Hyeon-Young Kim, Hyeon-Seong Lee, In-Hyeon Kim, Youngbae Kim, Moongi Ji, Songjin Oh, Doo-Young Kim, Wonjae Lee, Sung-Hwan Kim and Man-Jeong Paik
Int. J. Mol. Sci. 2022, 23(5), 2748; https://doi.org/10.3390/ijms23052748 - 02 Mar 2022
Cited by 5 | Viewed by 2553
Abstract
(1) Background: Progression of chronic obstructive pulmonary disease (COPD) leads to irreversible lung damage and inflammatory responses; however, biomarker discovery for monitoring of COPD progression remains challenging. (2) Methods: This study evaluated the metabolic mechanisms and potential biomarkers of COPD through the integrated [...] Read more.
(1) Background: Progression of chronic obstructive pulmonary disease (COPD) leads to irreversible lung damage and inflammatory responses; however, biomarker discovery for monitoring of COPD progression remains challenging. (2) Methods: This study evaluated the metabolic mechanisms and potential biomarkers of COPD through the integrated analysis and receiver operating characteristic (ROC) analysis of metabolic changes in lung, plasma, and urine, and changes in morphological characteristics and pulmonary function in a model of PPE/LPS-induced COPD exacerbation. (3) Results: Metabolic changes in the lungs were evaluated as metabolic reprogramming to counteract the changes caused by the onset of COPD. In plasma, several combinations of phenylalanine, 3-methylhistidine, and polyunsaturated fatty acids have been proposed as potential biomarkers; the α-aminobutyric acid/histidine ratio has also been reported, which is a novel candidate biomarker for COPD. In urine, a combination of succinic acid, isocitric acid, and pyruvic acid has been proposed as a potential biomarker. (4) Conclusions: This study proposed potential biomarkers in plasma and urine that reflect altered lung metabolism in COPD, concurrently with the evaluation of the COPD exacerbation model induced by PPE plus LPS administration. Therefore, understanding these integrative mechanisms provides new insights into the diagnosis, treatment, and severity assessment of COPD. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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26 pages, 3546 KiB  
Article
Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection
by Ivana Rubić, Richard Burchmore, Stefan Weidt, Clement Regnault, Josipa Kuleš, Renata Barić Rafaj, Tomislav Mašek, Anita Horvatić, Martina Crnogaj, Peter David Eckersall, Predrag Novak and Vladimir Mrljak
Int. J. Mol. Sci. 2022, 23(3), 1575; https://doi.org/10.3390/ijms23031575 - 29 Jan 2022
Cited by 6 | Viewed by 3297
Abstract
Canine babesiosis is an important tick-borne disease worldwide, caused by parasites of the Babesia genus. Although the disease process primarily affects erythrocytes, it may also have multisystemic consequences. The goal of this study was to explore and characterize the serum metabolome, by identifying [...] Read more.
Canine babesiosis is an important tick-borne disease worldwide, caused by parasites of the Babesia genus. Although the disease process primarily affects erythrocytes, it may also have multisystemic consequences. The goal of this study was to explore and characterize the serum metabolome, by identifying potential metabolites and metabolic pathways in dogs naturally infected with Babesia canis using liquid and gas chromatography coupled to mass spectrometry. The study included 12 dogs naturally infected with B. canis and 12 healthy dogs. By combining three different analytical platforms using untargeted and targeted approaches, 295 metabolites were detected. The untargeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) metabolomics approach identified 64 metabolites, the targeted UHPLC-MS/MS metabolomics approach identified 205 metabolites, and the GC-MS metabolomics approach identified 26 metabolites. Biological functions of differentially abundant metabolites indicate the involvement of various pathways in canine babesiosis including the following: glutathione metabolism; alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; cysteine and methionine metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis. This study confirmed that host–pathogen interactions could be studied by metabolomics to assess chemical changes in the host, such that the differences in serum metabolome between dogs with B. canis infection and healthy dogs can be detected with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) methods. Our study provides novel insight into pathophysiological mechanisms of B. canis infection. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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Review

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19 pages, 388 KiB  
Review
On the Relevance of Soft Tissue Sarcomas Metabolic Landscape Mapping
by Miguel Esperança-Martins, Iola F.Duarte, Mara Rodrigues, Joaquim Soares do Brito, Dolores López-Presa, Luís Costa, Isabel Fernandes and Sérgio Dias
Int. J. Mol. Sci. 2022, 23(19), 11430; https://doi.org/10.3390/ijms231911430 - 28 Sep 2022
Cited by 1 | Viewed by 1662
Abstract
Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a “fit for all” principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies [...] Read more.
Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a “fit for all” principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies that seek to decipher the sarcomagenesis mechanisms. There is an urge to improve STS diagnosis precision, refine STS classification criteria, and increase the capability of identifying STS prognostic biomarkers. Single-omics and multi-omics studies may play a key role on decodifying sarcomagenesis. Metabolomics provides a singular insight, either as a single-omics approach or as part of a multi-omics strategy, into the metabolic adaptations that support sarcomagenesis. Although STS metabolome is scarcely characterized, untargeted and targeted metabolomics approaches employing different data acquisition methods such as mass spectrometry (MS), MS imaging, and nuclear magnetic resonance (NMR) spectroscopy provided important information, warranting further studies. New chromatographic, MS, NMR-based, and flow cytometry-based methods will offer opportunities to therapeutically target metabolic pathways and to monitorize the response to such metabolic targeting therapies. Here we provide a comprehensive review of STS omics applications, comprising a detailed analysis of studies focused on the metabolic landscape of these tumors. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
22 pages, 2404 KiB  
Review
Applications of Metabolomics in Calcium Metabolism Disorders in Humans
by Beata Podgórska, Marta Wielogórska-Partyka, Joanna Godzień, Julia Siemińska, Michał Ciborowski, Małgorzata Szelachowska, Adam Krętowski and Katarzyna Siewko
Int. J. Mol. Sci. 2022, 23(18), 10407; https://doi.org/10.3390/ijms231810407 - 08 Sep 2022
Cited by 6 | Viewed by 2160
Abstract
The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, [...] Read more.
The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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19 pages, 1048 KiB  
Review
An Overview of the Latest Metabolomics Studies on Atopic Eczema with New Directions for Study
by Jamie Afghani, Claudia Traidl-Hoffmann, Philippe Schmitt-Kopplin, Matthias Reiger and Constanze Mueller
Int. J. Mol. Sci. 2022, 23(15), 8791; https://doi.org/10.3390/ijms23158791 - 08 Aug 2022
Cited by 5 | Viewed by 2897
Abstract
Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are not fully understood. Metabolomics, the analysis of small molecules in the skin produced [...] Read more.
Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are not fully understood. Metabolomics, the analysis of small molecules in the skin produced by the host and microbes, opens a window to observe the mechanisms of the disease which then may lead to new drug targets for AE treatment. Here, we review the latest advances in AE metabolomics, highlighting both the lipid and non-lipid molecules, along with reviewing the metabolites currently known to reside in the skin. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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20 pages, 1013 KiB  
Review
Current Knowledge in Skin Metabolomics: Updates from Literature Review
by Alessia Paganelli, Valeria Righi, Elisabetta Tarentini and Cristina Magnoni
Int. J. Mol. Sci. 2022, 23(15), 8776; https://doi.org/10.3390/ijms23158776 - 07 Aug 2022
Cited by 7 | Viewed by 2535
Abstract
Metabolomic profiling is an emerging field consisting of the measurement of metabolites in a biological system. Since metabolites can vary in relation to different stimuli, specific metabolic patterns can be closely related to a pathological process. In the dermatological setting, skin metabolomics can [...] Read more.
Metabolomic profiling is an emerging field consisting of the measurement of metabolites in a biological system. Since metabolites can vary in relation to different stimuli, specific metabolic patterns can be closely related to a pathological process. In the dermatological setting, skin metabolomics can provide useful biomarkers for the diagnosis, prognosis, and therapy of cutaneous disorders. The main goal of the present review is to present a comprehensive overview of the published studies in skin metabolomics. A search for journal articles focused on skin metabolomics was conducted on the MEDLINE, EMBASE, Cochrane, and Scopus electronic databases. Only research articles with electronically available English full text were taken into consideration. Studies specifically focused on cutaneous microbiomes were also excluded from the present search. A total of 97 papers matched all the research criteria and were therefore considered for the present work. Most of the publications were focused on inflammatory dermatoses and immune-mediated cutaneous disorders. Skin oncology also turned out to be a relevant field in metabolomic research. Only a few papers were focused on infectious diseases and rarer genetic disorders. All the major metabolomic alterations published so far in the dermatological setting are described extensively in this review. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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17 pages, 1626 KiB  
Review
Unraveling the Rewired Metabolism in Lung Cancer Using Quantitative NMR Metabolomics
by Karolien Vanhove, Elien Derveaux, Liesbet Mesotten, Michiel Thomeer, Maarten Criel, Hanne Mariën and Peter Adriaensens
Int. J. Mol. Sci. 2022, 23(10), 5602; https://doi.org/10.3390/ijms23105602 - 17 May 2022
Cited by 3 | Viewed by 2528
Abstract
Lung cancer cells are well documented to rewire their metabolism and energy production networks to enable proliferation and survival in a nutrient-poor and hypoxic environment. Although metabolite profiling of blood plasma and tissue is still emerging in omics approaches, several techniques have shown [...] Read more.
Lung cancer cells are well documented to rewire their metabolism and energy production networks to enable proliferation and survival in a nutrient-poor and hypoxic environment. Although metabolite profiling of blood plasma and tissue is still emerging in omics approaches, several techniques have shown potential in cancer diagnosis. In this paper, the authors describe the alterations in the metabolic phenotype of lung cancer patients. In addition, we focus on the metabolic cooperation between tumor cells and healthy tissue. Furthermore, the authors discuss how metabolomics could improve the management of lung cancer patients. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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14 pages, 2375 KiB  
Review
Cerebrospinal Fluid Metabolome in Parkinson’s Disease and Multiple System Atrophy
by Do Hyeon Kwon, Ji Su Hwang, Seok Gi Kim, Yong Eun Jang, Tae Hwan Shin and Gwang Lee
Int. J. Mol. Sci. 2022, 23(3), 1879; https://doi.org/10.3390/ijms23031879 - 07 Feb 2022
Cited by 8 | Viewed by 3526
Abstract
Parkinson’s disease (PD) and multiple system atrophy (MSA) belong to the neurodegenerative group of synucleinopathies; differential diagnosis between PD and MSA is difficult, especially at early stages, owing to their clinical and biological similarities. Thus, there is a pressing need to identify metabolic [...] Read more.
Parkinson’s disease (PD) and multiple system atrophy (MSA) belong to the neurodegenerative group of synucleinopathies; differential diagnosis between PD and MSA is difficult, especially at early stages, owing to their clinical and biological similarities. Thus, there is a pressing need to identify metabolic biomarkers for these diseases. The metabolic profile of the cerebrospinal fluid (CSF) is reported to be altered in PD and MSA; however, the altered metabolites remain unclear. We created a single network with altered metabolites in PD and MSA based on the literature and assessed biological functions, including metabolic disorders of the nervous system, inflammation, concentration of ATP, and neurological disorder, through bioinformatics methods. Our in-silico prediction-based metabolic networks are consistent with Parkinsonism events. Although metabolomics approaches provide a more quantitative understanding of biochemical events underlying the symptoms of PD and MSA, limitations persist in covering molecules related to neurodegenerative disease pathways. Thus, omics data, such as proteomics and microRNA, help understand the altered metabolomes mechanism. In particular, integrated omics and machine learning approaches will be helpful to elucidate the pathological mechanisms of PD and MSA. This review discusses the altered metabolites between PD and MSA in the CSF and omics approaches to discover diagnostic biomarkers. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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16 pages, 610 KiB  
Review
Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning
by Isabelle Alldritt, Paul L. Greenhaff and Daniel J. Wilkinson
Int. J. Mol. Sci. 2021, 22(24), 13575; https://doi.org/10.3390/ijms222413575 - 17 Dec 2021
Cited by 11 | Viewed by 4661
Abstract
Muscle deconditioning impairs both locomotor function and metabolic health, and is associated with reduced quality life and increased mortality rates. Despite an appreciation of the existence of phenomena such as muscle anabolic resistance, mitophagy, and insulin resistance with age and disease in humans, [...] Read more.
Muscle deconditioning impairs both locomotor function and metabolic health, and is associated with reduced quality life and increased mortality rates. Despite an appreciation of the existence of phenomena such as muscle anabolic resistance, mitophagy, and insulin resistance with age and disease in humans, little is known about the mechanisms responsible for these negative traits. With the complexities surrounding these unknowns and the lack of progress to date in development of effective interventions, there is a need for alternative approaches. Metabolomics is the study of the full array of metabolites within cells or tissues, which collectively constitute the metabolome. As metabolomics allows for the assessment of the cellular metabolic state in response to physiological stimuli, any chronic change in the metabolome is likely to reflect adaptation in the physiological phenotype of an organism. This, therefore, provides a holistic and unbiased approach that could be applied to potentially uncover important novel facets in the pathophysiology of muscle decline in ageing and disease, as well as identifying prognostic markers of those at risk of decline. This review will aim to highlight the current knowledge and potential impact of metabolomics in the study of muscle mass loss and deconditioning in humans and will highlight key areas for future research. Full article
(This article belongs to the Special Issue Metabolomics in Health and Disease)
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