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Metabolites
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Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches
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Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches

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

Deadline for manuscript submissions: closed (30 August 2020) | Viewed by 23621

Special Issue Editors

Dr. Timothy Garrett

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Guest Editor
Department of Medicine, Division of Environmental Medicine, University of Louisville, Louisville, KY 40202, USA
Interests: metabolomics; lipidomics; mass spectrometry; imaging; instrumentation
Dr. Donald H Chace

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Guest Editor
Medolac Laboratories, Boulder City, NV 89005, USA
Interests: newborn screeening; tandem mass spectrometry; neonatology; disease diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the past decade, metabolomic and lipidomic approaches have grown rapidly both from a technical perspective and from a disease diagnosis perspective. These approaches are now considered the first approach to begin to identify biomarkers related to many diseases, both human and plant. This Special Issue of Metabolites is titled “Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches” and is focused on analytical advances, applied research, and novel informatics methods that can be harnessed to tackle the identification of biomarkers in disease states. Manuscripts that tackle the challenges of identification of unknown diseases are also critical for this area of disease diagnostics, as we often encounter the unknown when studying a new disorder.

Dr. Timothy Garrett
Dr. Donald Chace
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
  • Lipidomics
  • Disease diagnostics
  • Biomarker identification

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Published Papers (6 papers)

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Research

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11 pages, 1485 KiB  
Article
Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses
by Di Yu, Qiuhui Xuan, Chaoqi Zhang, Chunxiu Hu, Yanli Li, Xinjie Zhao, Shasha Liu, Feifei Ren, Yi Zhang, Lina Zhou and Guowang Xu
Metabolites 2020, 10(12), 478; https://doi.org/10.3390/metabo10120478 - 24 Nov 2020
Cited by 20 | Viewed by 3001
Abstract
Gliomas are the most aggressive phenotypes of brain tumors and are classified into four grades according to the malignancy degree by the World Health Organization. Metabolic profiling can provide an overview of metabolic reprogramming at a specific stage of tumor initiation and development. [...] Read more.
Gliomas are the most aggressive phenotypes of brain tumors and are classified into four grades according to the malignancy degree by the World Health Organization. Metabolic profiling can provide an overview of metabolic reprogramming at a specific stage of tumor initiation and development. Studies about metabolic alterations related to different grades of gliomas are helpful to understand the molecular mechanism for progression of glioma. In the current study, metabolomics and lipidomics analyses based on chromatography-mass spectrometry were performed on different grades of glioma tissues. Differential metabolites between glioma and para-tumor tissues were studied and used as the basis to explore metabolic alterations related to glioma grading. It was found that short-chain acylcarnitines were elevated, whereas lysophosphatidylethanolamines (LPEs) were decreased in high-grade gliomas. Furthermore, the gene expression of short/branched-chain acyl-coenzyme dehydrogenase (ACADSB), which is involved in fatty acid oxidation, was found down-regulated with glioma progression by analyzing related genes and pathways. In addition, LPE metabolism showed a significant difference among different grades of gliomas. These important metabolic pathways related to glioma progression may provide potential clues for further study on the mechanisms and treatment of glioma. Full article
(This article belongs to the Special Issue Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches)
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20 pages, 4177 KiB  
Article
One-Year Effects of Omega-3 Treatment on Fatty Acids, Oxylipins, and Related Bioactive Lipids and Their Associations with Clinical Lipid and Inflammatory Biomarkers: Findings from a Substudy of the Vitamin D and Omega-3 Trial (VITAL)
by Olga V. Demler, Yanyan Liu, Heike Luttmann-Gibson, Jeramie D. Watrous, Kim A. Lagerborg, Hesam Dashti, Franco Giulianini, Mallory Heath, Carlos A. Camargo, Jr., William S. Harris, Jay G. Wohlgemuth, Allen M. Andres, Saumya Tivari, Tao Long, Mahan Najhawan, Khoi Dao, James G. Prentice, Julia A. Larsen, Olivia I. Okereke, Karen H. Costenbader, Julie E. Buring, JoAnn E. Manson, Susan Cheng, Mohit Jain and Samia Moraadd Show full author list remove Hide full author list
Metabolites 2020, 10(11), 431; https://doi.org/10.3390/metabo10110431 - 27 Oct 2020
Cited by 18 | Viewed by 4358
Abstract
Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and [...] Read more.
Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 individuals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women’s Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) < 0.05 in VITAL200, validated (p-values < 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids. N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits. Full article
(This article belongs to the Special Issue Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches)
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11 pages, 768 KiB  
Article
Metabolomic Alteration in the Mouse Distal Colonic Mucosa after Oral Gavage with Oxalobacter formigenes
by Casey A. Chamberlain, Marguerite Hatch and Timothy J. Garrett
Metabolites 2020, 10(10), 405; https://doi.org/10.3390/metabo10100405 - 13 Oct 2020
Cited by 6 | Viewed by 3639
Abstract
Oxalobacter formigenes has been investigated for years due to its proposed ability to produce a secretagogue compound that initiates net intestinal oxalate secretion, thereby theoretically reducing circulating oxalate and risk of kidney stone formation. Strains which have been shown to exhibit this function [...] Read more.
Oxalobacter formigenes has been investigated for years due to its proposed ability to produce a secretagogue compound that initiates net intestinal oxalate secretion, thereby theoretically reducing circulating oxalate and risk of kidney stone formation. Strains which have been shown to exhibit this function in vivo across native tissue include the human strain, HC1, and the wild rat strain, OxWR. While previous work on these secretagogue-relevant strains has focused on profiling their metabolome and lipidome in vitro, efforts to characterize their influence on host intestinal mucosal biochemistry in vivo are yet to be reported. Much work has been done over the years with O. formigenes in relation to the secretagogue hypothesis, but it has never been clearly demonstrated that this microorganism is capable of inducing metabolic changes in native host tissue, which would be expected with the production of a transport-inducing compound. In this work, we show how the distal colonic mucosal metabolomic profile in a mouse model exhibited significant changes in the levels of a variety of metabolites as a result of oral gavage with O. formigenes HC1. Among these significant metabolites was nicotinic acid, an essential nutrient shown in past work to be produced in the gut by the native microbiome. Our finding that the in vivo biochemical state of the distal colon was altered with O. formigenes lends support to the secretagogue hypothesis and serves as a pioneering step in characterizing the biochemical interplay between O. formigenes and the mammalian host. Full article
(This article belongs to the Special Issue Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches)
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15 pages, 1154 KiB  
Article
Targeted Metabolomic Profiling of Total Fatty Acids in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry
by Anas Al Aidaros, Charu Sharma, Claus-Dieter Langhans, Jürgen G. Okun, Georg F. Hoffmann, Majed Dasouki, Pranesh Chakraborty, Fatma Aljasmi and Osama Y. Al-Dirbashi
Metabolites 2020, 10(10), 400; https://doi.org/10.3390/metabo10100400 - 9 Oct 2020
Cited by 6 | Viewed by 3215
Abstract
This article reports a targeted metabolomic method for total plasma fatty acids (FAs) of clinical or nutritional relevance. Thirty-six saturated, unsaturated, or branched-chain FAs with a chain length of C8-C28 were quantified using reversed-phase liquid chromatography-tandem mass spectrometry. FAs in plasma (10 μL) [...] Read more.
This article reports a targeted metabolomic method for total plasma fatty acids (FAs) of clinical or nutritional relevance. Thirty-six saturated, unsaturated, or branched-chain FAs with a chain length of C8-C28 were quantified using reversed-phase liquid chromatography-tandem mass spectrometry. FAs in plasma (10 μL) were acid-hydrolyzed, extracted, and derivatized with DAABD-AE (4-[2-(N,N-Dimethylamino)ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole) at 60 °C for 1 h. Derivatization resulted in a staggering nine orders of magnitude higher sensitivity compared to underivatized analytes. FAs were measured by multiple-reaction monitoring using stable isotope internal standards. With physiological and pathological analyte levels in mind, linearity was established using spiked plasma. Intra-day (n = 15) and inter-day (n = 20) imprecisions expressed as variation coefficient were ≤10.2% with recovery ranging between 94.5–106.4%. Limits of detection and limit of quantitation ranged between 4.2–14.0 and 15.1–51.3 pmol per injection, respectively. Age-stratified reference intervals were established in four categories: <1 month, 1–12 month, 1–18 year, and >18 year. This method was assessed using samples from patients with disorders affecting FAs metabolism. For the first time, C28:0 and C28:0/C22:0 ratio were evaluated as novel disease biomarkers. This method can potentially be utilized in diagnosing patients with inborn errors of metabolism, chronic disease risk estimation, or nutritional applications. Full article
(This article belongs to the Special Issue Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches)
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Review

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17 pages, 347 KiB  
Review
Emerging Role of Metabolomics in Ovarian Cancer Diagnosis
by Asia Saorin, Emanuela Di Gregorio, Gianmaria Miolo, Agostino Steffan and Giuseppe Corona
Metabolites 2020, 10(10), 419; https://doi.org/10.3390/metabo10100419 - 19 Oct 2020
Cited by 32 | Viewed by 4099
Abstract
Ovarian cancer is considered a silent killer due to the lack of clear symptoms and efficient diagnostic tools that often lead to late diagnoses. Over recent years, the impelling need for proficient biomarkers has led researchers to consider metabolomics, an emerging omics science [...] Read more.
Ovarian cancer is considered a silent killer due to the lack of clear symptoms and efficient diagnostic tools that often lead to late diagnoses. Over recent years, the impelling need for proficient biomarkers has led researchers to consider metabolomics, an emerging omics science that deals with analyses of the entire set of small-molecules (≤1.5 kDa) present in biological systems. Metabolomics profiles, as a mirror of tumor–host interactions, have been found to be useful for the analysis and identification of specific cancer phenotypes. Cancer may cause significant metabolic alterations to sustain its growth, and metabolomics may highlight this, making it possible to detect cancer in an early phase of development. In the last decade, metabolomics has been widely applied to identify different metabolic signatures to improve ovarian cancer diagnosis. The aim of this review is to update the current status of the metabolomics research for the discovery of new diagnostic metabolomic biomarkers for ovarian cancer. The most promising metabolic alterations are discussed in view of their potential biological implications, underlying the issues that limit their effective clinical translation into ovarian cancer diagnostic tools. Full article
(This article belongs to the Special Issue Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches)
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30 pages, 723 KiB  
Review
Association between Metabolites and the Risk of Lung Cancer: A Systematic Literature Review and Meta-Analysis of Observational Studies
by Kian Boon Lee, Lina Ang, Wai-Ping Yau and Wei Jie Seow
Metabolites 2020, 10(9), 362; https://doi.org/10.3390/metabo10090362 - 5 Sep 2020
Cited by 17 | Viewed by 4555
Abstract
Globally, lung cancer is the most prevalent cancer type. However, screening and early detection is challenging. Previous studies have identified metabolites as promising lung cancer biomarkers. This systematic literature review and meta-analysis aimed to identify metabolites associated with lung cancer risk in observational [...] Read more.
Globally, lung cancer is the most prevalent cancer type. However, screening and early detection is challenging. Previous studies have identified metabolites as promising lung cancer biomarkers. This systematic literature review and meta-analysis aimed to identify metabolites associated with lung cancer risk in observational studies. The literature search was performed in PubMed and EMBASE databases, up to 31 December 2019, for observational studies on the association between metabolites and lung cancer risk. Heterogeneity was assessed using the I2 statistic and Cochran’s Q test. Meta-analyses were performed using either a fixed-effects or random-effects model, depending on study heterogeneity. Fifty-three studies with 297 metabolites were included. Most identified metabolites (252 metabolites) were reported in individual studies. Meta-analyses were conducted on 45 metabolites. Five metabolites (cotinine, creatinine riboside, N-acetylneuraminic acid, proline and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene) and five metabolite groups (total 3-hydroxycotinine, total cotinine, total nicotine, total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (sum of concentrations of the metabolite and its glucuronides), and total nicotine equivalent (sum of total 3-hydroxycotinine, total cotinine and total nicotine)) were associated with higher lung cancer risk, while three others (folate, methionine and tryptophan) were associated with lower lung cancer risk. Significant heterogeneity was detected across most studies. These significant metabolites should be further evaluated as potential biomarkers for lung cancer. Full article
(This article belongs to the Special Issue Identification of Disease Biomarkers by Metabolomic and Lipidomic Approaches)
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