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Metabolites
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Metabolomic Analysis of Plasma
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Metabolomic Analysis of Plasma

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Advances in Metabolomics".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 14536

Special Issue Editors

Prof. Paolo Follesa

E-Mail Website
Guest Editor
Department of Life and Environment Sciences, Section of Neuroscience and Anthropology and Center of Excellence for Neurobiology of Dependence, University of Cagliari, 09042 Monserrato, Italy
Interests: neuroscience; drug resistance; drug of abuse; neurotransmitters
Dr. Claudia Fattuoni

E-Mail Website
Guest Editor
Department of Chemical and Geological Sciences, University of Cagliari, 09042 Monserrato, Italy
Interests: metabolomics; GC-MS; Organic chemistry; organic synthesis

Special Issue Information

Dear Colleagues,

Metabolomics has proved to be one of the hot research topics of the last twenty years; the enormous interest in its potential in the interpretation of biochemical perturbations on living organisms led to more than 5700 WOS indexed publications in 2019. Many research fields found benefit from metabolomic analysis, both by NMR or mass platforms: medicine, biology, bothany, zoology, and so on. The wide interest and application of metabolomics may lead to a plethora of different protocols and methodologies: the need for accurate identification of metabolites and the standardization of procedures is required. Plasma metabolomics, both from human or animal subjects, is one of the most important and informative, due to the intrinsic nature of this biofluid. Research on plasma metabolomics, mainly or partially focused on metabolite identification, is the object of this Special Issue.

Prof. Paolo Follesa
Dr. Claudia Fattuoni
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • Metabolomics
  • Plasma
  • NMR
  • GC-MS
  • LC-MS
  • Metabolites
  • Biomarkers
  • Identification
  • Optimization

Published Papers (7 papers)

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Research

13 pages, 815 KiB  
Article
Effects of Chronic Bifidobacteria Administration in Adult Male Rats on Plasma Metabolites: A Preliminary Metabolomic Study
by Francesca Biggio, Claudia Fattuoni, Maria Cristina Mostallino and Paolo Follesa
Metabolites 2022, 12(8), 762; https://doi.org/10.3390/metabo12080762 - 18 Aug 2022
Viewed by 1612
Abstract
Probiotics are live microorganisms distributed in the gastrointestinal tract that confer health benefits to the host when administered in adequate amounts. Bifidobacteria have been widely tested as a therapeutic strategy in the prevention and treatment of a broad spectrum of gastrointestinal disorders as [...] Read more.
Probiotics are live microorganisms distributed in the gastrointestinal tract that confer health benefits to the host when administered in adequate amounts. Bifidobacteria have been widely tested as a therapeutic strategy in the prevention and treatment of a broad spectrum of gastrointestinal disorders as well as in the regulation of the “microbiota-gut-brain axis”. Metabolomic techniques can provide details in the study of molecular metabolic mechanisms involved in Bifidobacteria function through the analysis of metabolites that positively contribute to human health. This study was focused on the effects of the chronic assumption of a mixture of Bifidobacteria in adult male rats using a metabolomic approach. Plasma samples were collected at the end of treatment and analyzed with a gas chromatography-mass spectrometry (GC-MS) platform. Partial least square discriminant analysis (PLS-DA) was performed to compare the metabolic pattern in control and probiotic-treated rats. Our results show, in probiotic-treated animals, an increase in metabolites involved in the energetic cycle, such as glucose, erythrose, creatinine, taurine and glycolic acid, as well as 3-hydroxybutyric acid. This is an important metabolite of short-chain fatty acids (SCFA) with multitasking roles in energy circuit balance, and it has also been proposed to have a key role in the prevention and treatment of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Metabolomic Analysis of Plasma)
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16 pages, 2389 KiB  
Article
HPLC–(Q)-TOF-MS-Based Study of Plasma Metabolic Profile Differences Associated with Age in Pediatric Population Using an Animal Model
by Oihane E. Albóniga, Oskar González-Mendia, María E. Blanco and Rosa M. Alonso
Metabolites 2022, 12(8), 739; https://doi.org/10.3390/metabo12080739 - 11 Aug 2022
Cited by 1 | Viewed by 1354
Abstract
A deep knowledge about the biological development of children is essential for appropriate drug administration and dosage in pediatrics. In this sense, the best approximation to study organ maturation is the analysis of tissue samples, but it requires invasive methods. For this reason, [...] Read more.
A deep knowledge about the biological development of children is essential for appropriate drug administration and dosage in pediatrics. In this sense, the best approximation to study organ maturation is the analysis of tissue samples, but it requires invasive methods. For this reason, surrogate matrices should be explored. Among them, plasma emerges as a potential alternative since it represents a snapshot of global organ metabolism. In this work, plasma metabolic profiles from piglets of different ages (newborns, infants, and children) obtained by HPLC–(Q)-TOF-MS at positive and negative ionization modes were studied. Improved clustering within groups was achieved using multiblock principal component analysis compared to classical principal component analysis. Furthermore, the separation observed among groups was better resolved by using partial least squares-discriminant analysis, which was validated by bootstrapping and permutation testing. Thanks to univariate analysis, 13 metabolites in positive and 21 in negative ionization modes were found to be significant to discriminate the three groups of piglets. From these features, an acylcarnitine and eight glycerophospholipids were annotated and identified as metabolites of interest. The findings indicate that there is a relevant change with age in lipid metabolism in which lysophosphatidylcholines and lysophoshatidylethanolamines play an important role. Full article
(This article belongs to the Special Issue Metabolomic Analysis of Plasma)
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14 pages, 1419 KiB  
Article
Circulating Metabolites in Relation to the Kidney Allograft Function in Posttransplant Patients
by Eva Baranovicova, Matej Vnucak, Karol Granak, Jan Lehotsky, Nina Kadasova, Juraj Miklusica and Ivana Dedinska
Metabolites 2022, 12(7), 661; https://doi.org/10.3390/metabo12070661 - 18 Jul 2022
Cited by 1 | Viewed by 1673
Abstract
End-stage kidney disease is preferably treated by kidney transplantation. The suboptimal function of the allograft often results in misbalances in kidney-controlled processes and requires long-term monitoring of allograft function and viability. As the kidneys are organs with a very high metabolomic rate, a [...] Read more.
End-stage kidney disease is preferably treated by kidney transplantation. The suboptimal function of the allograft often results in misbalances in kidney-controlled processes and requires long-term monitoring of allograft function and viability. As the kidneys are organs with a very high metabolomic rate, a metabolomics approach is suitable to describe systematic changes in post-transplant patients and has great potential for monitoring allograft function, which has not been described yet. In this study, we used blood plasma samples from 55 patients after primary kidney transplantation identically treated with immunosuppressants with follow-up 50 months in the mean after surgery and evaluated relative levels of basal plasma metabolites detectable by NMR spectroscopy. We were looking for the correlations between circulating metabolites levels and allograft performance and allograft rejection features. Our results imply a quantitative relationship between restricted renal function, insufficient hydroxylation of phenylalanine to tyrosine, lowered renal glutamine utilization, shifted nitrogen balance, and other alterations that are not related exclusively to the metabolism of the kidney. No link between allograft function and energy metabolism can be concluded, as no changes were found for glucose, glycolytic intermediates, and 3-hydroxybutyrate as a ketone body representative. The observed changes are to be seen as a superposition of changes in the comprehensive inter-organ metabolic exchange, when the restricted function of one organ may induce compensatory effects or cause secondary alterations. Particular differences in plasma metabolite levels in patients with acute cellular and antibody-mediated allograft rejection were considered rather to be related to the loss of kidney function than to the molecular mechanism of graft rejection since they largely follow the alterations observed by restricted allograft function. In the end, we showed using a simple mathematical model, multilinear regression, that the basal plasmatic metabolites correlated with allograft function expressed by the level of glomerular filtration rate (with creatinine: p-value = 4.0 × 10−26 and r = 0.94, without creatinine: p-value = 3.2 × 10−22 and r = 0.91) make the noninvasive estimation of the allograft function feasible. Full article
(This article belongs to the Special Issue Metabolomic Analysis of Plasma)
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12 pages, 3015 KiB  
Article
Alterations in Blood Plasma Metabolome of Patients with Lesniowski-Crohn’s Disease Shortly after Surgical Treatment—Pilot Study
by Jakub Idkowiak, Grażyna Kubiak-Tomaszewska, Paulina Gątarek, Łukasz Marczak, Joanna Kałużna-Czaplińska, Wiesław Tarnowski, Mariusz Uryszek and Barbara Bobrowska-Korczak
Metabolites 2022, 12(6), 529; https://doi.org/10.3390/metabo12060529 - 08 Jun 2022
Viewed by 1663
Abstract
Lesniowski-Crohn’s disease (CD) is a type of chronic inflammatory bowel disease (IBD) of uncertain etiology. Initially, pharmacological management is undertaken; however, surgical intervention is necessary to improve life quality and relieve symptoms in most cases. Here changes are reported in blood metabolome that [...] Read more.
Lesniowski-Crohn’s disease (CD) is a type of chronic inflammatory bowel disease (IBD) of uncertain etiology. Initially, pharmacological management is undertaken; however, surgical intervention is necessary to improve life quality and relieve symptoms in most cases. Here changes are reported in blood metabolome that occurred three days after the ileo-colic region resection in the case of seven patients. Alterations are observed in levels of metabolites associated with multiple mitochondrial pathways, based on the Metabolite Set Enrichment Analysis, reflecting a high energy demand in the post-operative period. As most of these metabolites are also essential nutrients supplied from foods, we believe that our results might contribute to the discussion on perioperative nutrition’s role in enhanced recovery. Full article
(This article belongs to the Special Issue Metabolomic Analysis of Plasma)
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13 pages, 5050 KiB  
Article
Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study
by Patricia A. Da Cunha, Diana Nitusca, Luisa Matos Do Canto, Rency S. Varghese, Habtom W. Ressom, Shawna Willey, Catalin Marian and Bassem R. Haddad
Metabolites 2022, 12(5), 447; https://doi.org/10.3390/metabo12050447 - 17 May 2022
Cited by 2 | Viewed by 2305
Abstract
Breast cancer (BC) is one of the leading causes of cancer mortality in women worldwide, and therefore, novel biomarkers for early disease detection are critically needed. We performed herein an untargeted plasma metabolomic profiling of 55 BC patients and 55 healthy controls (HC) [...] Read more.
Breast cancer (BC) is one of the leading causes of cancer mortality in women worldwide, and therefore, novel biomarkers for early disease detection are critically needed. We performed herein an untargeted plasma metabolomic profiling of 55 BC patients and 55 healthy controls (HC) using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). Pre-processed data revealed 2494 ions in total. Data matrices’ paired t-tests revealed 792 ions (both positive and negative) which presented statistically significant changes (FDR < 0.05) in intensity levels between cases versus controls. Metabolites identified with putative names via MetaboQuest using MS/MS and mass-based approaches included amino acid esters (i.e., N-stearoyl tryptophan, L-arginine ethyl ester), dipeptides (ile-ser, met-his), nitrogenous bases (i.e., uracil derivatives), lipid metabolism-derived molecules (caproleic acid), and exogenous compounds from plants, drugs, or dietary supplements. LASSO regression selected 16 metabolites after several variables (TNM Stage, Grade, smoking status, menopausal status, and race) were adjusted. A predictive conditional logistic regression model on the 16 LASSO selected ions provided a high diagnostic performance with an area-under-the-curve (AUC) value of 0.9729 (95% CI 0.96–0.98) on all 55 samples. This study proves that BC possesses a specific metabolic signature that could be exploited as a novel metabolomics-based approach for BC detection and characterization. Future studies of large-scale cohorts are needed to validate these findings. Full article
(This article belongs to the Special Issue Metabolomic Analysis of Plasma)
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11 pages, 16738 KiB  
Article
A Nuclear Magnetic Resonance Spectroscopy Method in Characterization of Blood Metabolomics for Alzheimer’s Disease
by JianXiang Weng, Isabella H. Muti, Anya B. Zhong, Pia Kivisäkk, Bradley T. Hyman, Steven E. Arnold and Leo L. Cheng
Metabolites 2022, 12(2), 181; https://doi.org/10.3390/metabo12020181 - 15 Feb 2022
Cited by 5 | Viewed by 2501
Abstract
There is currently a crucial need for improved diagnostic techniques and targeted treatment methods for Alzheimer’s disease (AD), a disease which impacts millions of elderly individuals each year. Metabolomic analysis has been proposed as a potential methodology to better investigate and understand the [...] Read more.
There is currently a crucial need for improved diagnostic techniques and targeted treatment methods for Alzheimer’s disease (AD), a disease which impacts millions of elderly individuals each year. Metabolomic analysis has been proposed as a potential methodology to better investigate and understand the progression of this disease. In this report, we present our AD metabolomics results measured with high resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) on human blood plasma samples obtained from AD and non-AD subjects. Our study centers on developments of AD and non-AD metabolomics differentiating models with procedures of quality assurance (QA) and quality control (QC) through pooled samples. Our findings suggest that analysis of blood plasma samples using HRMAS NMR has the potential to differentiate between diseased and healthy subjects, which has important clinical implications for future improvements in AD diagnosis methodologies. Full article
(This article belongs to the Special Issue Metabolomic Analysis of Plasma)
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14 pages, 3298 KiB  
Article
Plasma Metabolomics in a Nonhuman Primate Model of Abdominal Radiation Exposure
by Se-Ran Jun, Marjan Boerma, Zulema Udaondo, Sasha Richardson, Karla D. Thrall, Isabelle R. Miousse, John Seng, Rupak Pathak and Martin Hauer-Jensen
Metabolites 2021, 11(8), 540; https://doi.org/10.3390/metabo11080540 - 13 Aug 2021
Viewed by 2136
Abstract
The acute radiation syndrome is defined in large part by radiation injury in the hematopoietic and gastrointestinal (GI) systems. To identify new pathways involved in radiation-induced GI injury, this study assessed dose- and time-dependent changes in plasma metabolites in a nonhuman primate model [...] Read more.
The acute radiation syndrome is defined in large part by radiation injury in the hematopoietic and gastrointestinal (GI) systems. To identify new pathways involved in radiation-induced GI injury, this study assessed dose- and time-dependent changes in plasma metabolites in a nonhuman primate model of whole abdominal irradiation. Male and female adult Rhesus monkeys were exposed to 6 MV photons to the abdomen at doses ranging between 8 and 14 Gy. At time points from 1 to 60 days after irradiation, plasma samples were collected and subjected to untargeted metabolomics. With the limited sample size of females, different discovery times after irradiation between males and females were observed in metabolomics pattern. Detailed analyses are restricted to only males for the discovery power. Radiation caused an increase in fatty acid oxidation and circulating levels of corticosteroids which may be an indication of physiological stress, and amino acids, indicative of a cellular repair response. The largest changes were observed at days 9 and 10 post-irradiation, with most returning to baseline at day 30. In addition, dysregulated metabolites involved in amino acid pathways, which might indicate changes in the microbiome, were detected. In conclusion, abdominal irradiation in a nonhuman primate model caused a plasma metabolome profile indicative of GI injury. These results point to pathways that may be targeted for intervention or used as early indicators of GI radiation injury. Moreover, our results suggest that effects are sex-specific and that interventions may need to be tailored accordingly. Full article
(This article belongs to the Special Issue Metabolomic Analysis of Plasma)
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