Next Issue
Volume 10, October
Previous Issue
Volume 10, August

Metabolites, Volume 10, Issue 9 (September 2020) – 44 articles

Cover Story (view full-size image): Preterm birth (PTB) is a serious concern for neonate and maternal health, increasing the risk of mortality and morbidity. Several measures have been introduced for monitoring of PTB that offer just superficial information and are inadequate for confirmation of the PTB-causing agent. During pregnancy, hormonal/metabolic changes and consumption of high-protein/carbohydrate diets cause dysregulation, and gut microbiota alteration leads to dysbiosis of the vaginal microbiota profile. This dysbiosis of the vaginal microbiota, which occurs occasionally, is considered the most common cause of ascending vaginal infection. This dysbiosis directly impacts the production of pathogenic microbiota metabolites by changing the vaginal pH and inducing the release of proinflammatory cytokines (IL-6, IL-8, etc.) and immunological cells that might be responsible for PTB. View this paper.
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
Order results
Result details
Select all
Export citation of selected articles as:
Article
Evaluation of Sample Preparation Methods for Inter-Laboratory Metabolomics Investigation of Streptomyces lividans TK24
Metabolites 2020, 10(9), 379; https://doi.org/10.3390/metabo10090379 - 22 Sep 2020
Viewed by 826
Abstract
In the past two decades, metabolomics has proved to be a valuable tool with many potential applications in different areas of science. However, there are still some challenges that need to be addressed, particularly for multicenter studies. These challenges are mainly attributed to [...] Read more.
In the past two decades, metabolomics has proved to be a valuable tool with many potential applications in different areas of science. However, there are still some challenges that need to be addressed, particularly for multicenter studies. These challenges are mainly attributed to various sources of fluctuation and unwanted variations that can be introduced at pre-analytical, analytical, and/or post-analytical steps of any metabolomics experiment. Thus, this study aimed at using Streptomyces lividans TK24 as the model organism in a cross-laboratory experiment in Manchester and Leuven to evaluate the reproducibility of a standard sample preparation method, and determine the optimal sample format (cell extract or quenched biomass) required to preserve the metabolic profile of the cells during cross-lab sample transportation and storage. Principal component analysis (PCA) scores plot of the gas chromatography-mass spectrometry (GC-MS) data from both laboratories displayed clear growth-dependent clustering patterns which was in agreement with the Procrustes analysis findings. In addition, the data generated in Manchester displayed tight clustering of cell pellets (quenched biomass) and metabolite extracts, confirming the stability of both sample formats during the transportation and storage period. Full article
Show Figures

Graphical abstract

Article
Comparison of Three Untargeted Data Processing Workflows for Evaluating LC-HRMS Metabolomics Data
Metabolites 2020, 10(9), 378; https://doi.org/10.3390/metabo10090378 - 21 Sep 2020
Cited by 6 | Viewed by 1574
Abstract
The evaluation of liquid chromatography high-resolution mass spectrometry (LC-HRMS) raw data is a crucial step in untargeted metabolomics studies to minimize false positive findings. A variety of commercial or open source software solutions are available for such data processing. This study aims to [...] Read more.
The evaluation of liquid chromatography high-resolution mass spectrometry (LC-HRMS) raw data is a crucial step in untargeted metabolomics studies to minimize false positive findings. A variety of commercial or open source software solutions are available for such data processing. This study aims to compare three different data processing workflows (Compound Discoverer 3.1, XCMS Online combined with MetaboAnalyst 4.0, and a manually programmed tool using R) to investigate LC-HRMS data of an untargeted metabolomics study. Simple but highly standardized datasets for evaluation were prepared by incubating pHLM (pooled human liver microsomes) with the synthetic cannabinoid A-CHMINACA. LC-HRMS analysis was performed using normal- and reversed-phase chromatography followed by full scan MS in positive and negative mode. MS/MS spectra of significant features were subsequently recorded in a separate run. The outcome of each workflow was evaluated by its number of significant features, peak shape quality, and the results of the multivariate statistics. Compound Discoverer as an all-in-one solution is characterized by its ease of use and seems, therefore, suitable for simple and small metabolomic studies. The two open source solutions allowed extensive customization but particularly, in the case of R, made advanced programming skills necessary. Nevertheless, both provided high flexibility and may be suitable for more complex studies and questions. Full article
(This article belongs to the Special Issue New Psychoactive Substances - Metabolism and Metabolomics)
Show Figures

Figure 1

Review
Exercise May Affect Metabolism in Cancer-Related Cognitive Impairment
Metabolites 2020, 10(9), 377; https://doi.org/10.3390/metabo10090377 - 20 Sep 2020
Viewed by 1181
Abstract
Cancer-related cognitive impairment (CRCI) is a significant comorbidity for cancer patients and survivors. Physical activity (PA) has been found to be a strong gene modulator that can induce structural and functional changes in the brain. PA and exercise reduce the risk of cancer [...] Read more.
Cancer-related cognitive impairment (CRCI) is a significant comorbidity for cancer patients and survivors. Physical activity (PA) has been found to be a strong gene modulator that can induce structural and functional changes in the brain. PA and exercise reduce the risk of cancer development and progression and has been shown to help in overcoming post-treatment syndromes. Exercise plays a role in controlling cancer progression through direct effects on cancer metabolism. In this review, we highlight several priorities for improving studies on CRCI in patients and its underlying potential metabolic mechanisms. Full article
(This article belongs to the Special Issue Cancer Metabolomic 2020)
Show Figures

Graphical abstract

Article
Towards Standardization of Data Normalization Strategies to Improve Urinary Metabolomics Studies by GC×GC-TOFMS
Metabolites 2020, 10(9), 376; https://doi.org/10.3390/metabo10090376 - 19 Sep 2020
Cited by 5 | Viewed by 1094
Abstract
Urine is a popular biofluid for metabolomics studies due to its simple, non-invasive collection and its availability in large quantities, permitting frequent sampling, replicate analyses, and sample banking. The biggest disadvantage with using urine is that it exhibits significant variability in concentration and [...] Read more.
Urine is a popular biofluid for metabolomics studies due to its simple, non-invasive collection and its availability in large quantities, permitting frequent sampling, replicate analyses, and sample banking. The biggest disadvantage with using urine is that it exhibits significant variability in concentration and composition within an individual over relatively short periods of time (arising from various external factors and internal processes regulating the body’s water and solute content). In treating the data from urinary metabolomics studies, one must account for the natural variability of urine concentrations to avoid erroneous data interpretation. Amongst various proposed approaches to account for broadly varying urine sample concentrations, normalization to creatinine has been widely accepted and is most commonly used. MS total useful signal (MSTUS) is another normalization method that has been recently reported for mass spectrometry (MS)-based metabolomics studies. Herein, we explored total useful peak area (TUPA), a modification of MSTUS that is applicable to GC×GC-TOFMS (and data from other separations platforms), for sample normalization in urinary metabolomics studies. Performance of TUPA was compared to the two most common normalization approaches, creatinine adjustment and Total Peak Area (TPA) normalization. Each normalized dataset was evaluated using Principal Component Analysis (PCA). The results showed that TUPA outperformed alternative normalization methods to overcome urine concentration variability. Results also conclusively demonstrate the risks in normalizing data to creatinine. Full article
Show Figures

Figure 1

Article
Chasing the Major Sphingolipids on Earth: Automated Annotation of Plant Glycosyl Inositol Phospho Ceramides by Glycolipidomics
Metabolites 2020, 10(9), 375; https://doi.org/10.3390/metabo10090375 - 19 Sep 2020
Cited by 3 | Viewed by 1465
Abstract
Glycosyl inositol phospho ceramides (GIPCs) are the major sphingolipids on earth, as they account for a considerable fraction of the total lipids in plants and fungi, which in turn represent a large portion of the biomass on earth. Despite their obvious importance, GIPC [...] Read more.
Glycosyl inositol phospho ceramides (GIPCs) are the major sphingolipids on earth, as they account for a considerable fraction of the total lipids in plants and fungi, which in turn represent a large portion of the biomass on earth. Despite their obvious importance, GIPC analysis remains challenging due to the lack of commercial standards and automated annotation software. In this work, we introduce a novel GIPC glycolipidomics workflow based on reversed-phase ultra-high pressure liquid chromatography coupled to high-resolution mass spectrometry. For the first time, automated GIPC assignment was performed using the open-source software Lipid Data Analyzer (LDA), based on platform-independent decision rules. Four different plant samples (salad, spinach, raspberry, and strawberry) were analyzed and the results revealed 64 GIPCs based on accurate mass, characteristic MS2 fragments and matching retention times. Relative quantification using lactosyl ceramide for internal standardization revealed GIPC t18:1/h24:0 as the most abundant species in all plants. Depending on the plant sample, GIPCs contained mainly amine, N-acetylamine or hydroxyl residues. Most GIPCs revealed a Hex-HexA-IPC core and contained a ceramide part with a trihydroxylated t18:0 or a t18:1 long chain base and hydroxylated fatty acid chains ranging from 16 to 26 carbon atoms in length (h16:0–h26:0). Interestingly, four GIPCs containing t18:2 were observed in the raspberry sample, which was not reported so far. The presented workflow supports the characterization of different plant samples by automatic GIPC assignment, potentially leading to the identification of new GIPCs. For the first time, automated high-throughput profiling of these complex glycolipids is possible by liquid chromatography-high-resolution tandem mass spectrometry and subsequent automated glycolipid annotation based on decision rules. Full article
(This article belongs to the Special Issue Advances in Lipidomics: Biomedicine, Nutrients and Methodology)
Show Figures

Graphical abstract

Review
Metabolomic Profiling in Neuromyelitis Optica Spectrum Disorder Biomarker Discovery
Metabolites 2020, 10(9), 374; https://doi.org/10.3390/metabo10090374 - 18 Sep 2020
Cited by 3 | Viewed by 1134
Abstract
There is no specific test for diagnosing neuromyelitis optica spectrum disorder (NMOSD), a disabling autoimmune disease of the central nervous system. Instead, diagnosis relies on ruling out other related disorders with overlapping clinical symptoms. An urgency for NMOSD biomarker discovery is underscored by [...] Read more.
There is no specific test for diagnosing neuromyelitis optica spectrum disorder (NMOSD), a disabling autoimmune disease of the central nervous system. Instead, diagnosis relies on ruling out other related disorders with overlapping clinical symptoms. An urgency for NMOSD biomarker discovery is underscored by adverse responses to treatment following misdiagnosis and poor prognosis following the delayed onset of treatment. Pathogenic autoantibiotics that target the water channel aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) contribute to NMOSD pathology. The importance of early diagnosis between AQP4-Ab+ NMOSD, MOG-Ab+ NMOSD, AQP4-Ab MOG-Ab NMOSD, and related disorders cannot be overemphasized. Here, we provide a comprehensive data collection and analysis of the currently known metabolomic perturbations and related proteomic outcomes of NMOSD. We highlight short chain fatty acids, lipoproteins, amino acids, and lactate as candidate diagnostic biomarkers. Although the application of metabolomic profiling to individual NMOSD patient care shows promise, more research is needed. Full article
Show Figures

Figure 1

Article
Metabolic Profiling of a Porcine Combat Trauma-Injury Model Using NMR and Multi-Mode LC-MS Metabolomics—A Preliminary Study
Metabolites 2020, 10(9), 373; https://doi.org/10.3390/metabo10090373 - 16 Sep 2020
Cited by 1 | Viewed by 989
Abstract
Profiles of combat injuries worldwide have shown that penetrating trauma is one of the most common injuries sustained during battle. This is usually accompanied by severe bleeding or hemorrhage. If the soldier does not bleed to death, he may eventually succumb to complications [...] Read more.
Profiles of combat injuries worldwide have shown that penetrating trauma is one of the most common injuries sustained during battle. This is usually accompanied by severe bleeding or hemorrhage. If the soldier does not bleed to death, he may eventually succumb to complications arising from trauma hemorrhagic shock (THS). THS occurs when there is a deficiency of oxygen reaching the organs due to excessive blood loss. It can trigger massive metabolic derangements and an overwhelming inflammatory response, which can subsequently lead to the failure of organs and possibly death. A better understanding of the acute metabolic changes occurring after THS can help in the development of interventional strategies, as well as lead to the identification of potential biomarkers for rapid diagnosis of hemorrhagic shock and organ failure. In this preliminary study, a metabolomic approach using the complementary platforms of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled with mass spectrometry (LC-MS) was used to determine the metabolic changes occurring in a porcine model of combat trauma injury comprising of penetrating trauma to a limb with hemorrhagic shock. Several metabolites associated with the acute-phase reaction, inflammation, energy depletion, oxidative stress, and possible renal dysfunction were identified to be significantly changed after a thirty-minute shock period. Full article
(This article belongs to the Special Issue Animal and Cellular Models in Metabolomics Research)
Show Figures

Graphical abstract

Article
Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages
Metabolites 2020, 10(9), 372; https://doi.org/10.3390/metabo10090372 - 15 Sep 2020
Cited by 10 | Viewed by 2193
Abstract
Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a [...] Read more.
Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent. Full article
Show Figures

Graphical abstract

Review
Vitamin D Metabolism and Profiling in Veterinary Species
Metabolites 2020, 10(9), 371; https://doi.org/10.3390/metabo10090371 - 15 Sep 2020
Cited by 3 | Viewed by 1158
Abstract
The demand for vitamin D analysis in veterinary species is increasing with the growing knowledge of the extra-skeletal role vitamin D plays in health and disease. The circulating 25-hydroxyvitamin-D (25(OH)D) metabolite is used to assess vitamin D status, and the benefits of analysing [...] Read more.
The demand for vitamin D analysis in veterinary species is increasing with the growing knowledge of the extra-skeletal role vitamin D plays in health and disease. The circulating 25-hydroxyvitamin-D (25(OH)D) metabolite is used to assess vitamin D status, and the benefits of analysing other metabolites in the complex vitamin D pathway are being discovered in humans. Profiling of the vitamin D pathway by liquid chromatography tandem mass spectrometry (LC-MS/MS) facilitates simultaneous analysis of multiple metabolites in a single sample and over wide dynamic ranges, and this method is now considered the gold-standard for quantifying vitamin D metabolites. However, very few studies report using LC-MS/MS for the analysis of vitamin D metabolites in veterinary species. Given the complexity of the vitamin D pathway and the similarities in the roles of vitamin D in health and disease between humans and companion animals, there is a clear need to establish a comprehensive, reliable method for veterinary analysis that is comparable to that used in human clinical practice. In this review, we highlight the differences in vitamin D metabolism between veterinary species and the benefits of measuring vitamin D metabolites beyond 25(OH)D. Finally, we discuss the analytical challenges in profiling vitamin D in veterinary species with a focus on LC-MS/MS methods. Full article
(This article belongs to the Special Issue Steroid Profiling in Health and Disease)
Show Figures

Figure 1

Article
Effect of Added Dietary Betaine and Soluble Fiber on Metabolites and Fecal Microbiome in Dogs with Early Renal Disease
Metabolites 2020, 10(9), 370; https://doi.org/10.3390/metabo10090370 - 15 Sep 2020
Viewed by 1078
Abstract
Renal diets are recommended for dogs with chronic kidney disease (CKD). This study examined the effects of foods with added betaine and fiber on the plasma and fecal metabolome and fecal microbiome in dogs with early stage CKD. At baseline, several metabolites differed [...] Read more.
Renal diets are recommended for dogs with chronic kidney disease (CKD). This study examined the effects of foods with added betaine and fiber on the plasma and fecal metabolome and fecal microbiome in dogs with early stage CKD. At baseline, several metabolites differed between healthy dogs and those with CKD. Dogs with CKD (n = 28) received a control food, low soluble fiber plus betaine food (0.5% betaine, 0.39% oat beta-glucan, and 0.27% short-chain fructooligosaccharides (scFOS)), or high soluble fiber plus betaine food (0.5% betaine, 0.59% oat beta-glucan, and 0.41% scFOS) each for 10 weeks in different sequences. Consumption of test foods led to several favorable, significant changes in the plasma metabolome, including decreases of several uremic toxins and other deleterious metabolites, and increases in favorable metabolites compared with the control food. Only 7 fecal metabolites significantly changed with consumption of the test foods compared with the control food, largely increases in polyphenols and lignans. Few changes were seen in the fecal microbiome, though some taxa that significantly changed in response to the test foods have beneficial effects on health, with some negatively correlating with uremic toxins. Overall, foods with added betaine and soluble fiber showed positive effects on the plasma and fecal metabolomes. Full article
(This article belongs to the Special Issue Metabolomic Applications in Animal Science Volume 2)
Show Figures

Figure 1

Article
Composition of Intracellular and Cell Wall-Bound Phlorotannin Fractions in Fucoid Algae Indicates Specific Functions of These Metabolites Dependent on the Chemical Structure
Metabolites 2020, 10(9), 369; https://doi.org/10.3390/metabo10090369 - 11 Sep 2020
Cited by 2 | Viewed by 847
Abstract
Accumulation of biologically active metabolites is a specific feature of plant biochemistry, directing the use of plants in numerous applications in the pharmaceutical and food industries. Among these substances, the plethora of phenolic compounds has attracted particular interest among researchers. Here, we report [...] Read more.
Accumulation of biologically active metabolites is a specific feature of plant biochemistry, directing the use of plants in numerous applications in the pharmaceutical and food industries. Among these substances, the plethora of phenolic compounds has attracted particular interest among researchers. Here, we report on new findings in phlorotannin research, a large group of multifunctional phenolic substances, produced in brown algae. Comprehensive LC-MS profiling of three algal species allowed us to depict the complex pattern of this structurally diverse compound group across different tissues and subcellular compartments. We compiled more than 30 different phlorotannin series in one sample and used accurate mass spectrometry to assign tentative structures to the observed ions based on the confirmed sum formulas. From that, we found that acetylation, hydroxylation, and oxidation are likely to be the most common in vivo modifications to phlorotannins. Using an alternative data mining strategy to cope with extensive coelution and structural isomers, we quantitatively compared the intensity of different phlorotannin series in species, tissues, and subcellular compartments to learn more about their physiological functions. The structure and intra-thallus profiles of cell wall-bound phlorotannins were studied here for the first time. We suggest that one of the major dibenzodioxin-type phlorotannin series may exclusively target integration into the cell wall of fucoid algae. Full article
(This article belongs to the Special Issue Seaweeds Metabolites Volume 2)
Show Figures

Figure 1

Article
Atom Identifiers Generated by a Neighborhood-Specific Graph Coloring Method Enable Compound Harmonization across Metabolic Databases
Metabolites 2020, 10(9), 368; https://doi.org/10.3390/metabo10090368 - 11 Sep 2020
Cited by 2 | Viewed by 1202
Abstract
Metabolic flux analysis requires both a reliable metabolic model and reliable metabolic profiles in characterizing metabolic reprogramming. Advances in analytic methodologies enable production of high-quality metabolomics datasets capturing isotopic flux. However, useful metabolic models can be difficult to derive due to the lack [...] Read more.
Metabolic flux analysis requires both a reliable metabolic model and reliable metabolic profiles in characterizing metabolic reprogramming. Advances in analytic methodologies enable production of high-quality metabolomics datasets capturing isotopic flux. However, useful metabolic models can be difficult to derive due to the lack of relatively complete atom-resolved metabolic networks for a variety of organisms, including human. Here, we developed a neighborhood-specific graph coloring method that creates unique identifiers for each atom in a compound facilitating construction of an atom-resolved metabolic network. What is more, this method is guaranteed to generate the same identifier for symmetric atoms, enabling automatic identification of possible additional mappings caused by molecular symmetry. Furthermore, a compound coloring identifier derived from the corresponding atom coloring identifiers can be used for compound harmonization across various metabolic network databases, which is an essential first step in network integration. With the compound coloring identifiers, 8865 correspondences between KEGG (Kyoto Encyclopedia of Genes and Genomes) and MetaCyc compounds are detected, with 5451 of them confirmed by other identifiers provided by the two databases. In addition, we found that the Enzyme Commission numbers (EC) of reactions can be used to validate possible correspondence pairs, with 1848 unconfirmed pairs validated by commonality in reaction ECs. Moreover, we were able to detect various issues and errors with compound representation in KEGG and MetaCyc databases by compound coloring identifiers, demonstrating the usefulness of this methodology for database curation. Full article
(This article belongs to the Section Bioinformatics and Data Analysis)
Show Figures

Graphical abstract

Article
Metabolomics-Based Study of the Effect of Raw Materials to the End Product of Tempe—An Indonesian Fermented Soybean
Metabolites 2020, 10(9), 367; https://doi.org/10.3390/metabo10090367 - 11 Sep 2020
Cited by 2 | Viewed by 1230
Abstract
Tempe is a fermented soybean food from Indonesia, made by inoculating Rhizopus spp. onto cooked and dehulled soybean. Tempe has been a part of Indonesian culture since the 16th century and is now produced globally as a highly nutritious plant-based food. Despite a [...] Read more.
Tempe is a fermented soybean food from Indonesia, made by inoculating Rhizopus spp. onto cooked and dehulled soybean. Tempe has been a part of Indonesian culture since the 16th century and is now produced globally as a highly nutritious plant-based food. Despite a longstanding history on the production of tempe, very few studies have been reported to understand the effect of raw material to the end product metabolite composition. In this research, we applied GC/MS-based metabolite profiling to investigate the effect of various possible factors that might affect the final product (environmental factors, raw materials, and starter cultures). Representative samples were tempe produced by Indonesian industries, Japanese industries as well as laboratory made tempe. The results showed that both environmental factors and raw materials (soybean, water, and starter culture) contributed to the tempe metabolite profile. Here we found the possibility that starter cultures might play a greater role to determine the metabolite profiles compared to other tested factors. This research might provide useful insights for the larger scale industries to maintain the quality of tempe for the benefit of the consumers. Full article
(This article belongs to the Section Food Science)
Show Figures

Figure 1

Article
Lipidomic UPLC-MS/MS Profiles of Normal-Appearing White Matter Differentiate Primary and Secondary Progressive Multiple Sclerosis
Metabolites 2020, 10(9), 366; https://doi.org/10.3390/metabo10090366 - 08 Sep 2020
Cited by 1 | Viewed by 1364
Abstract
Multiple sclerosis (MS) is a neurodegenerative inflammatory disease where an autoimmune response to components of the central nervous system leads to a loss of myelin and subsequent neurological deterioration. People with MS can develop primary or secondary progressive disease (PPMS, SPMS) and differentiation [...] Read more.
Multiple sclerosis (MS) is a neurodegenerative inflammatory disease where an autoimmune response to components of the central nervous system leads to a loss of myelin and subsequent neurological deterioration. People with MS can develop primary or secondary progressive disease (PPMS, SPMS) and differentiation of the specific differences in the pathogenesis of these two courses, at the molecular level, is currently unclear. Recently, lipidomics studies using human biofluids, mainly plasma and cerebrospinal fluid, have highlighted a possible role for lipids in the initiation and progression of MS. However, there is a lack of lipidomics studies in MS on CNS tissues, such as normal-appearing white matter (NAWM), where local inflammation initially occurs. Herein, we developed an untargeted reverse phase ultra-performance liquid chromatography time of flight tandem mass spectrometry (RP-UPLC-TOF MSE)-based workflow, in combination with multivariate and univariate statistical analysis, to assess significant differences in lipid profiles in brain NAWM from post-mortem cases of PPMS, SPMS and controls. Groups of eight control, nine PPMS and seven SPMS NAWM samples were used. Correlation analysis of the identified lipids by RP-UPLC-TOF MSE was undertaken to remove those lipids that correlated with age, gender and post-mortem interval as confounding factors. We demonstrate that there is a significantly altered lipid profile of control cases compared with MS cases and that progressive disease, PPMS and SPMS, can be differentiated on the basis of the lipidome of NAWM with good sensitivity, specificity and prediction accuracy based on receiver operating characteristic (ROC) curve analysis. Metabolic pathway analysis revealed that the most altered lipid pathways between PPMS and SPMS were glycerophospholipid metabolism, glycerophosphatidyl inositol (GPI) anchor synthesis and linoleic acid metabolism. Further understanding of the impact of these lipid alterations described herein associated with progression will provide an increased understanding of the mechanisms underpinning progression and highlight possible new therapeutic targets. Full article
Show Figures

Graphical abstract

Article
Effect of Sample Storage Conditions on Measurements of Salivary Cotinine Levels
Metabolites 2020, 10(9), 365; https://doi.org/10.3390/metabo10090365 - 08 Sep 2020
Viewed by 716
Abstract
Information on smoking exposure obtained with self-reports may be inaccurate. Cotinine has a large half-life and its salivary levels correlate well with plasmatic levels. The influence of storage conditions on the validity and precision of salivary cotinine assessments has rarely been evaluated. Here, [...] Read more.
Information on smoking exposure obtained with self-reports may be inaccurate. Cotinine has a large half-life and its salivary levels correlate well with plasmatic levels. The influence of storage conditions on the validity and precision of salivary cotinine assessments has rarely been evaluated. Here, smokers donated saliva samples, which were sent for immediate analysis, mail posting, storage at 4 °C for 30 or 90 days, or storage at −20 °C for 30 or 90 days. Cotinine levels were determined using enzyme-linked immune-sorbent assay. Agreement of cotinine level measurements was assessed using Bland-Altman analyses. Average age (years), duration of smoking (years) and number of cigarettes smoked (/day) were 55.4 (±SD 9.4), 35.1 (±SD 11.3), and 15.3 (±SD 7.6). The mean immediate cotinine level was 457 ng/mL (range 11.3 to 1318 ng/mL). Mean cotinine levels in samples analyzed after delay ranged between 433 ng/mL (−20 °C 30 days) and 468 ng/mL (4 °C 30 days). A dose-response gradient was observed in the relationship between salivary cotinine level and self-reported smoking status. A good agreement between cotinine levels for all storage conditions compared with immediate analysis was observed, with average differences ranging from −11 to 24 ng/mL. Cotinine levels remained stable regardless of the tested condition. The stability of salivary cotinine may enable samples to be obtained in difficult-to-reach areas, reduce study costs, and improve the validity of the information on exposure to smoking. Full article
(This article belongs to the Section Pharmacology and Drug Metabolism)
Show Figures

Graphical abstract

Editorial
Metabolomics Applications in Children: A Right Way to Go
Metabolites 2020, 10(9), 364; https://doi.org/10.3390/metabo10090364 - 08 Sep 2020
Viewed by 701
Abstract
Metabolomics is a new science based on the study of the metabolome, representing the set of all the metabolites of a biological organism, which are the final products of its gene expression. Metabolomics appears to be a promising tool in perinatal studies, such [...] Read more.
Metabolomics is a new science based on the study of the metabolome, representing the set of all the metabolites of a biological organism, which are the final products of its gene expression. Metabolomics appears to be a promising tool in perinatal studies, such as hypoxic–ischemic encephalopathy (HIE), intrauterine growth restriction (IUGR), congenital infections, genetic diseases, neonatal nutrition. Full article
(This article belongs to the Special Issue Applications of Metabolomics in Maternal and Child Health)
Article
Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in Drosophila melanogaster
Metabolites 2020, 10(9), 363; https://doi.org/10.3390/metabo10090363 - 06 Sep 2020
Cited by 4 | Viewed by 1250
Abstract
In insect, pyruvate is generally the predominant oxidative substrate for mitochondria. This metabolite is transported inside mitochondria via the mitochondrial pyruvate carrier (MPC), but whether and how this transporter controls mitochondrial oxidative capacities in insects is still relatively unknown. Here, we characterize the [...] Read more.
In insect, pyruvate is generally the predominant oxidative substrate for mitochondria. This metabolite is transported inside mitochondria via the mitochondrial pyruvate carrier (MPC), but whether and how this transporter controls mitochondrial oxidative capacities in insects is still relatively unknown. Here, we characterize the importance of pyruvate transport as a metabolic control point for mitochondrial substrate oxidation in two genotypes of an insect model, Drosophila melanogaster, differently expressing MPC1, an essential protein for the MPC function. We evaluated the kinetics of pyruvate oxidation, mitochondrial oxygen consumption, metabolic profile, activities of metabolic enzymes, and climbing abilities of wild-type (WT) flies and flies harboring a deficiency in MPC1 (MPC1def). We hypothesized that MPC1 deficiency would cause a metabolic reprogramming that would favor the oxidation of alternative substrates. Our results show that the MPC1def flies display significantly reduced climbing capacity, pyruvate-induced oxygen consumption, and enzymatic activities of pyruvate kinase, alanine aminotransferase, and citrate synthase. Moreover, increased proline oxidation capacity was detected in MPC1def flies, which was associated with generally lower levels of several metabolites, and particularly those involved in amino acid catabolism such as ornithine, citrulline, and arginosuccinate. This study therefore reveals the flexibility of mitochondrial substrate oxidation allowing Drosophila to maintain cellular homeostasis. Full article
(This article belongs to the Section Cell Metabolism)
Show Figures

Figure 1

Review
Association between Metabolites and the Risk of Lung Cancer: A Systematic Literature Review and Meta-Analysis of Observational Studies
Metabolites 2020, 10(9), 362; https://doi.org/10.3390/metabo10090362 - 05 Sep 2020
Cited by 5 | Viewed by 1370
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
Show Figures

Figure 1

Article
Low Molecular Weight Volatile Organic Compounds Indicate Grazing by the Marine Rotifer Brachionus plicatilis on the Microalgae Microchloropsis salina
Metabolites 2020, 10(9), 361; https://doi.org/10.3390/metabo10090361 - 04 Sep 2020
Cited by 2 | Viewed by 1028
Abstract
Microalgae produce specific chemicals indicative of stress and/or death. The aim of this study was to perform non-destructive monitoring of algal culture systems, in the presence and absence of grazers, to identify potential biomarkers of incipient pond crashes. Here, we report ten volatile [...] Read more.
Microalgae produce specific chemicals indicative of stress and/or death. The aim of this study was to perform non-destructive monitoring of algal culture systems, in the presence and absence of grazers, to identify potential biomarkers of incipient pond crashes. Here, we report ten volatile organic compounds (VOCs) that are robustly generated by the marine alga, Microchloropsis salina, in the presence and/or absence of the marine grazer, Brachionus plicatilis. We cultured M. salina with and without B. plicatilis and collected in situ volatile headspace samples using thermal desorption tubes over the course of several days. Data from four experiments were aggregated, deconvoluted, and chromatographically aligned to determine VOCs with tentative identifications made via mass spectral library matching. VOCs generated by algae in the presence of actively grazing rotifers were confirmed via pure analytical standards to be pentane, 3-pentanone, 3-methylhexane, and 2-methylfuran. Six other VOCs were less specifically associated with grazing but were still commonly observed between the four replicate experiments. Through this work, we identified four biomarkers of rotifer grazing that indicate algal stress/death. This will aid machine learning algorithms to chemically define and diagnose algal mass production cultures and save algae cultures from imminent crash to make biofuel an alternative energy possibility. Full article
(This article belongs to the Section Environmental Science)
Show Figures

Graphical abstract

Article
An 1H NMR- and MS-Based Study of Metabolites Profiling of Garden Snail Helix aspersa Mucus
Metabolites 2020, 10(9), 360; https://doi.org/10.3390/metabo10090360 - 02 Sep 2020
Cited by 5 | Viewed by 992
Abstract
Metabolic profiling based on 1H nuclear magnetic resonance (NMR) spectroscopy was applied with the aim to investigate the functional role of the metabolites in lyophilized mucus from the garden snail Helix aspersa. Twenty metabolites were unambiguously identified by 1H, 1D [...] Read more.
Metabolic profiling based on 1H nuclear magnetic resonance (NMR) spectroscopy was applied with the aim to investigate the functional role of the metabolites in lyophilized mucus from the garden snail Helix aspersa. Twenty metabolites were unambiguously identified by 1H, 1D TOCSY, 2D J-resolved, 2D COSY, and 2D HSQC NMR spectra with water suppression. The metabolic profiles of two fractions with low molecular weight (Mw < 1 kDa and Mw < 3 kDa) are very similar. Metabolites with known antioxidant, antibacterial, and antimicrobial activity were detected by NMR metabolic analysis of mucus samples from Helix aspersa. Some of them were confirmed by mass spectrometric analysis. The primary structure of several peptides was identified in low molecular weight fractions (Mw < 1 kDa) by tandem mass spectrometry. Full article
Show Figures

Graphical abstract

Article
Potential Lipid Signatures for Diagnosis and Prognosis of Sepsis and Systemic Inflammatory Response Syndrome
Metabolites 2020, 10(9), 359; https://doi.org/10.3390/metabo10090359 - 01 Sep 2020
Cited by 1 | Viewed by 1099
Abstract
Systemic inflammatory response syndrome (SIRS) and sepsis are two conditions which are difficult to differentiate clinically and which are strongly impacted for prompt intervention. This study identified potential lipid signatures that are able to differentiate SIRS from sepsis and to predict prognosis. Forty-two [...] Read more.
Systemic inflammatory response syndrome (SIRS) and sepsis are two conditions which are difficult to differentiate clinically and which are strongly impacted for prompt intervention. This study identified potential lipid signatures that are able to differentiate SIRS from sepsis and to predict prognosis. Forty-two patients, including 21 patients with sepsis and 21 patients with SIRS, were involved in the study. Liquid chromatography coupled to mass spectrometry and multivariate statistical methods were used to determine lipids present in patient plasma. The obtained lipid signatures revealed 355 features for the negative ion mode and 297 for the positive ion mode, which were relevant for differential diagnosis of sepsis and SIRS. These lipids were also tested as prognosis predictors. Lastly, L-octanoylcarnitine was found to be the most promising lipid signature for both the diagnosis and prognosis of critically ill patients, with accuracies of 75% for both purposes. In short, we presented the determination of lipid signatures as a potential tool for differential diagnosis of sepsis and SIRS and prognosis of these patients. Full article
(This article belongs to the Section Metabolomic Profiling Technology)
Show Figures

Graphical abstract

Article
Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery
Metabolites 2020, 10(9), 358; https://doi.org/10.3390/metabo10090358 - 01 Sep 2020
Cited by 2 | Viewed by 980
Abstract
Background: Obstructive sleep apnea (OSA) is caused by partial or complete obstruction of the upper airways. Corrective surgeries aim at removing obstructions in the nasopharynx, oropharynx, and hypopharynx. OSA is associated with an increased risk of various metabolic diseases. Our objective was to [...] Read more.
Background: Obstructive sleep apnea (OSA) is caused by partial or complete obstruction of the upper airways. Corrective surgeries aim at removing obstructions in the nasopharynx, oropharynx, and hypopharynx. OSA is associated with an increased risk of various metabolic diseases. Our objective was to evaluate the effect of surgery on the plasma metabolome. Methods: This study included 39 OSA patients who underwent Multilevel Sleep Surgery (MLS). Clinical and anthropometric measures were taken at baseline and five months after surgery. Results: The mean Apnea-Hypopnea Index (AHI) significantly dropped from 22.0 ± 18.5 events/hour to 8.97 ± 9.57 events/hour (p-Value < 0.001). Epworth’s sleepiness Score (ESS) dropped from 12.8 ± 6.23 to 2.95 ± 2.40 (p-Value < 0.001), indicating the success of the surgery in treating OSA. Plasma levels of metabolites, phosphocholines (PC) PC.41.5, PC.42.3, ceremide (Cer) Cer.44.0, and triglyceride (TG) TG.53.6, TG.55.6 and TG.56.8 were decreased (p-Value < 0.05), whereas lysophosphatidylcholines (LPC) 20.0 and PC.39.3 were increased (p-Value < 0.05) after surgery. Conclusion: This study highlights the success of MLS in treating OSA. Treatment of OSA resulted in an improvement of the metabolic status that was characterized by decreased TG, PCs, and Cer metabolites after surgery, indicating that the success of the surgery positively impacted the metabolic status of these patients. Full article
(This article belongs to the Section Metabolomic Profiling Technology)
Show Figures

Figure 1

Article
Targeted Metabolic Profiling of Urine Highlights a Potential Biomarker Panel for the Diagnosis of Alzheimer’s Disease and Mild Cognitive Impairment: A Pilot Study
Metabolites 2020, 10(9), 357; https://doi.org/10.3390/metabo10090357 - 31 Aug 2020
Cited by 5 | Viewed by 1653
Abstract
The lack of sensitive and specific biomarkers for the early detection of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is a major hurdle to improving patient management. A targeted, quantitative metabolomics approach using both 1H NMR and mass spectrometry was employed [...] Read more.
The lack of sensitive and specific biomarkers for the early detection of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is a major hurdle to improving patient management. A targeted, quantitative metabolomics approach using both 1H NMR and mass spectrometry was employed to investigate the performance of urine metabolites as potential biomarkers for MCI and AD. Correlation-based feature selection (CFS) and least absolute shrinkage and selection operator (LASSO) methods were used to develop biomarker panels tested using support vector machine (SVM) and logistic regression models for diagnosis of each disease state. Metabolic changes were investigated to identify which biochemical pathways were perturbed as a direct result of MCI and AD in urine. Using SVM, we developed a model with 94% sensitivity, 78% specificity, and 78% AUC to distinguish healthy controls from AD sufferers. Using logistic regression, we developed a model with 85% sensitivity, 86% specificity, and an AUC of 82% for AD diagnosis as compared to cognitively healthy controls. Further, we identified 11 urinary metabolites that were significantly altered to include glucose, guanidinoacetate, urocanate, hippuric acid, cytosine, 2- and 3-hydroxyisovalerate, 2-ketoisovalerate, tryptophan, trimethylamine N oxide, and malonate in AD patients, which are also capable of diagnosing MCI, with a sensitivity value of 76%, specificity of 75%, and accuracy of 81% as compared to healthy controls. This pilot study suggests that urine metabolomics may be useful for developing a test capable of diagnosing and distinguishing MCI and AD from cognitively healthy controls. Full article
(This article belongs to the Special Issue Metabolomics in Human Tissues and Materials)
Show Figures

Figure 1

Review
Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update
Metabolites 2020, 10(9), 356; https://doi.org/10.3390/metabo10090356 - 31 Aug 2020
Cited by 3 | Viewed by 1066
Abstract
The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host [...] Read more.
The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins. Here, we review the role of cholesterol and other lipids in ssRNA+ infection. Full article
(This article belongs to the Special Issue Advances in Lipidomics: Biomedicine, Nutrients and Methodology)
Show Figures

Graphical abstract

Article
Plasma Lipid Profiling of Three Types of Drug-Induced Liver Injury in Japanese Patients: A Preliminary Study
Metabolites 2020, 10(9), 355; https://doi.org/10.3390/metabo10090355 - 31 Aug 2020
Cited by 3 | Viewed by 961
Abstract
Drug-induced liver injury (DILI) is a major adverse event caused by drug treatment, which can be categorized into three types: hepatocellular, mixed, and cholestatic. Although nearly every class of drugs can cause DILI, an overall understanding of lipid profiles in DILI patients is [...] Read more.
Drug-induced liver injury (DILI) is a major adverse event caused by drug treatment, which can be categorized into three types: hepatocellular, mixed, and cholestatic. Although nearly every class of drugs can cause DILI, an overall understanding of lipid profiles in DILI patients is lacking. We used lipidomics to analyze the plasma lipid profiles of patients to understand their hepatic pathophysiology and identify DILI biomarkers. We identified 463 lipids and compared their levels between the acute and recovery phases of the three types of DILI patients. Mixed and cholestatic types demonstrated specific plasma lipid alterations between the phases, but the hepatocellular type did not. Moreover, as specific indicators of mixed-type DILI, levels of several ceramides increased in the acute phase, while those of arachidonic acid-containing ether-linked phosphoglycerolipids decreased. In contrast, as specific indicators of cholestatic-type DILI, levels of palmitic acid-containing saturated or monounsaturated phosphatidylcholines increased in the acute phase, while those of arachidonic acid- or docosahexaenoic acid-containing ether-linked phosphoglycerolipids and phosphatidylinositols decreased. We also identified lipids with a relatively high capacity to discriminate the acute phase from the recovery phase and healthy subjects. These findings may help with understanding the pathophysiology of different DILI types and identify candidate biomarkers. Full article
(This article belongs to the Special Issue Advances in Lipidomics: Biomedicine, Nutrients and Methodology)
Show Figures

Figure 1

Article
Skeletal Muscle Angiopoietin-Like Protein 4 and Glucose Metabolism in Older Adults after Exercise and Weight Loss
Metabolites 2020, 10(9), 354; https://doi.org/10.3390/metabo10090354 - 31 Aug 2020
Cited by 1 | Viewed by 912
Abstract
Angiopoietin-like protein 4 (ANGPTL4) is an adipokine that plays an important role in energy homoeostasis and lipid and lipoprotein metabolism. This study was designed to determine the effect of an exercise plus weight loss intervention on ANGPTL4 expression and its relationship with metabolic [...] Read more.
Angiopoietin-like protein 4 (ANGPTL4) is an adipokine that plays an important role in energy homoeostasis and lipid and lipoprotein metabolism. This study was designed to determine the effect of an exercise plus weight loss intervention on ANGPTL4 expression and its relationship with metabolic health. Thirty-five obese sedentary men (n = 18) and postmenopausal women (n = 17), (X ± SEM, age: 61 ± 1 years, BMI: 31.3 ± 0.7 kg/m2, VO2max: 21.7 ± 0.9 L/kg/min) completed a 6 month program of 3×/week aerobic exercise and 1×/week dietary instruction to induce weight loss (AEX + WL). Participants underwent vastus lateralis muscle biopsies, a hyperinsulinemic–euglycemic clamp, oral glucose tolerance tests and body composition testing. Basal skeletal muscle ANGPTL4 mRNA was lower in men than women (p < 0.01). Peroxisome proliferator-activated receptor (PPAR) alpha (PPARα) mRNA expression was higher in men than women (p < 0.05). There were no significance changes in serum or skeletal muscle ANGPTL4 (basal or insulin-stimulated) or muscle PPARα mRNA expression after AEX + WL. Muscle mRNA ANGPTL4 is correlated with serum ANGPTL4 (r = 0.41, p < 0.05), body fat (r = 0.64, p < 0.0001), and glucose utilization (r = 0.38, p < 0.05). AEX + WL does not change basal or insulin-stimulated skeletal muscle ANGPTL4 mRNA expression, suggesting other factors contribute to improved insulin sensitivity after the loss of body fat and improved fitness. Full article
(This article belongs to the Special Issue Fatty Acid Metabolism)
Show Figures

Figure 1

Article
Characterization of Sunflower Oil Extracts from the Lichen Usnea barbata
Metabolites 2020, 10(9), 353; https://doi.org/10.3390/metabo10090353 - 31 Aug 2020
Cited by 3 | Viewed by 1178
Abstract
The increasing global emergence of multidrug resistant (MDR) pathogens is categorized as one of the most important health problems. Therefore, the discovery of novel antimicrobials is of the utmost importance. Lichens provide a rich source of natural products including unique polyketides and polyphenols. [...] Read more.
The increasing global emergence of multidrug resistant (MDR) pathogens is categorized as one of the most important health problems. Therefore, the discovery of novel antimicrobials is of the utmost importance. Lichens provide a rich source of natural products including unique polyketides and polyphenols. Many of them display pharmaceutical benefits. The aim of this study was directed towards the characterization of sunflower oil extracts from the fruticose lichen, Usnea barbata. The concentration of the major polyketide, usnic acid, was 1.6 mg/mL extract as determined by NMR analysis of the crude mixture corresponding to 80 mg per g of the dried lichen. The total phenolics and flavonoids were determined by photometric assays as 4.4 mg/mL (gallic acid equivalent) and 0.27 mg/mL (rutin equivalent) corresponding to 220 mg/g and 13.7 mg/g lichen, respectively. Gram-positive (e.g., Enterococcus faecalis) and Gram-negative bacteria, as well as clinical isolates of infected chickens were sensitive against these extracts as determined by agar diffusion tests. Most of these activities increased in the presence of zinc salts. The data suggest the potential usage of U. barbata extracts as natural additives and mild antibiotics in animal husbandry, especially against enterococcosis in poultry. Full article
(This article belongs to the Special Issue Metabolites: From Physiology to Pathology)
Show Figures

Graphical abstract

Article
Comparative Lipidomics of Different Yeast Species Associated to Drosophila suzukii
Metabolites 2020, 10(9), 352; https://doi.org/10.3390/metabo10090352 - 28 Aug 2020
Cited by 1 | Viewed by 1036
Abstract
Yeasts constitute a dietary source for the spotted wing drosophila (SWD) and produce compounds that attract these flies. The study of the chemical composition of the yeast communities associated with SWD should therefore help to understand the relationship between the biology of the [...] Read more.
Yeasts constitute a dietary source for the spotted wing drosophila (SWD) and produce compounds that attract these flies. The study of the chemical composition of the yeast communities associated with SWD should therefore help to understand the relationship between the biology of the insect and the yeast’s metabolism. In the present study, the lipidome of five yeast species isolated from grapes infested by SWD (three Hanseniaspora uvarum strains, Candida sp., Issatchenkia terricola, Metschnikowia pulcherrima and Saccharomycopsis vini) and a laboratory strain of Saccharomyces cerevisiae was explored using an untargeted approach. Additionally, the lipid profile of two species, S. cerevisiae and H. uvarum, which were reported to elicit different responses on SWD flies based on feeding and behavioral trials, was compared with a chemical enrichment approach. Overall, 171 lipids were annotated. The yeast species could be distinguished from each other based on their lipid profile, except for the three strains of H. uvarum, which were very similar to each other. The chemical enrichment analysis emphasized diversities between S. cerevisiae and H. uvarum, that could not be detected based on their global lipid profile. The information concerning differences between species in their lipidome may be of interest to future entomological studies concerning the yeast-insect interaction and could help to explain the responses of SWD to diverse yeast species. Full article
Show Figures

Graphical abstract

Article
Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome
Metabolites 2020, 10(9), 351; https://doi.org/10.3390/metabo10090351 - 28 Aug 2020
Cited by 5 | Viewed by 1126
Abstract
Gut microbiota plays essential roles in maintaining gut homeostasis. The composition of gut microbes and their metabolites are altered in response to diet and remedial agents such as antibiotics. However, little is known about the effect of antibiotics on the gut microbiota and [...] Read more.
Gut microbiota plays essential roles in maintaining gut homeostasis. The composition of gut microbes and their metabolites are altered in response to diet and remedial agents such as antibiotics. However, little is known about the effect of antibiotics on the gut microbiota and their volatile metabolites. In this study, we evaluated the impact of a moderate level of ampicillin treatment on volatile fatty acids (VFAs) of gut microbial cultures using an optimized real-time secondary electrospray ionization coupled with high-resolution mass spectrometry (SESI-HRMS). To evaluate the ionization efficiency, different types of electrospray solvents and concentrations of formic acid as an additive (0.01, 0.05, and 0.1%, v/v) were tested using VFAs standard mixture (C2–C7). As a result, the maximum SESI-HRMS signals of all studied m/z values were observed from water with 0.01% formic acid than those from the aqueous methanolic solutions. Optimal temperatures of sample inlet and ion chamber were set at 130 °C and 85 °C, respectively. SESI spray pressure at 0.5 bar generated the maximum intensity than other tested values. The optimized SESI-HRMS was then used for the analysis of VFAs in gut microbial cultures. We detected that the significantly elevated C4 and C7 VFAs in the headspace of gut microbial cultures six hours after ampicillin treatment (1 mg/L). In conclusion, our results suggested that the optimized SESI-HRMS method can be suitable for the analysis of VFAs from gut microbes in a rapid, sensitive, and non-invasive manner. Full article
(This article belongs to the Special Issue Volatile Metabolites’ New Frontier for Metabolomics)
Show Figures

Figure 1

Article
Diabetes Leads to Alterations in Normal Metabolic Transitions of Pregnancy as Revealed by Time-Course Metabolomics
Metabolites 2020, 10(9), 350; https://doi.org/10.3390/metabo10090350 - 27 Aug 2020
Cited by 4 | Viewed by 1145
Abstract
Women with diabetes during pregnancy are at increased risk of poor maternal and neonatal outcomes. Despite this, the effects of pre-gestational (PGDM) or gestational diabetes (GDM) on metabolism during pregnancy are not well understood. In this study, we utilized metabolomics to identify serum [...] Read more.
Women with diabetes during pregnancy are at increased risk of poor maternal and neonatal outcomes. Despite this, the effects of pre-gestational (PGDM) or gestational diabetes (GDM) on metabolism during pregnancy are not well understood. In this study, we utilized metabolomics to identify serum metabolic changes in women with and without diabetes during pregnancy and the cord blood at birth. We observed elevations in tricarboxylic acid (TCA) cycle intermediates, carbohydrates, ketones, and lipids, and a decrease in amino acids across gestation in all individuals. In early gestation, PGDM had elevations in branched-chain amino acids and sugars compared to controls, whereas GDM had increased lipids and decreased amino acids during pregnancy. In both GDM and PGDM, carbohydrate and amino acid pathways were altered, but in PGDM, hemoglobin A1c and isoleucine were significantly increased compared to GDM. Cord blood from GDM and PGDM newborns had similar increases in carbohydrates and choline metabolism compared to controls, and these alterations were not maternal in origin. Our results revealed that PGDM and GDM have distinct metabolic changes during pregnancy. A better understanding of diabetic metabolism during pregnancy can assist in improved management and development of therapeutics and help mitigate poor outcomes in both the mother and newborn. Full article
(This article belongs to the Special Issue Metabolomics Study in Women Health)
Show Figures

Figure 1

Previous Issue
Next Issue
Back to TopTop