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Arthritis Research & Therapy Jul 2020Several metabolomics studies have shed substantial light on the pathophysiological pathways underlying multiple diseases including systemic lupus erythematosus (SLE).... (Review)
Review
Several metabolomics studies have shed substantial light on the pathophysiological pathways underlying multiple diseases including systemic lupus erythematosus (SLE). This review takes stock of our current understanding of this field. We compare, collate, and investigate the metabolites in SLE patients and healthy volunteers, as gleaned from published metabolomics studies on SLE. In the surveyed primary reports, serum or plasma samples from SLE patients and healthy controls were assayed using mass spectrometry or nuclear magnetic resonance spectroscopy, and metabolites differentiating SLE from controls were identified. Collectively, the circulating metabolome in SLE is characterized by reduced energy substrates from glycolysis, Krebs cycle, fatty acid β oxidation, and glucogenic and ketogenic amino acid metabolism; enhanced activity of the urea cycle; decreased long-chain fatty acids; increased medium-chain and free fatty acids; and augmented peroxidation and inflammation. However, these findings should be interpreted with caution because several of the same metabolic pathways are also significantly influenced by the medications commonly used in SLE patients, common co-morbidities, and other factors including smoking and diet. In particular, whereas the metabolic alterations relating to inflammation, oxidative stress, lipid peroxidation, and glutathione generation do not appear to be steroid-dependent, the other metabolic changes may in part be influenced by steroids. To conclude, metabolomics studies of SLE and other rheumatic diseases ought to factor in the potential contributions of confounders such as medications, co-morbidities, smoking, and diet.
Topics: Humans; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Magnetic Resonance Spectroscopy; Metabolome; Metabolomics
PubMed: 32680552
DOI: 10.1186/s13075-020-02264-2 -
The Journal of Biological Chemistry Jul 2011Metabolomics is a data-based research strategy, the aims of which are to identify biomarker pictures of metabolic systems and metabolic perturbations and to formulate... (Review)
Review
Metabolomics is a data-based research strategy, the aims of which are to identify biomarker pictures of metabolic systems and metabolic perturbations and to formulate hypotheses to be tested. It involves the assay by mass spectrometry or NMR of many metabolites present in the biological system investigated. In this minireview, we outline studies in which metabolomics led to useful biomarkers of metabolic processes. We also illustrate how the discovery potential of metabolomics is enhanced by associating it with stable isotopic techniques.
Topics: Animals; Biomarkers; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolome; Metabolomics
PubMed: 21566142
DOI: 10.1074/jbc.R110.171405 -
PloS One 2018The potential of a metabolomics method to detect statistically significant perturbations in the metabolome of an organism is enhanced by excellent analytical precision,... (Comparative Study)
Comparative Study
The potential of a metabolomics method to detect statistically significant perturbations in the metabolome of an organism is enhanced by excellent analytical precision, unequivocal identification, and broad metabolomic coverage. While the former two metrics are usually associated with targeted metabolomics and the latter with non-targeted metabolomics, a systematic comparison of the performance of both approaches has not yet been carried out. The present work reports on the development and performance evaluation of separate targeted and non-targeted metabolomics methods. The targeted approach facilitated determination of 181 metabolites (quantitative analysis of 18 amino acids, 11 biogenic amines, 5 neurotransmitters, 5 nucleobases and semi-quantitative analysis of 50 carnitines, 83 phosphatidylcholines, and 9 sphingomyelins) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and flow injection-tandem mass spectrometry (FI-MS/MS). Method accuracy and/or precision were assessed using replicate samples of NIST SRM1950 as well as fish liver and brain tissue from Gilthead Bream (Sparus aurata). The non-target approach involved UPLC-high resolution (Orbitrap) mass spectrometry (UPLC-HRMS). Testing of ionization mode and stationary phase revealed that a combination of positive electrospray ionization and HILIC chromatography produced the largest number of chromatographic features during non-target analysis. Furthermore, an evaluation of 4 different sequence drift correction algorithms, and combinations thereof, revealed that batchCorr produced the best precision in almost every test. However, even following correction of non-target data for signal drift, the precision of targeted data was better, confirming our existing assumptions about the strengths of targeted metabolomics. Finally, the accuracy of the online MS2-library mzCloud was evaluated using reference standards for 38 different metabolites. This is among the few studies that have systematically evaluated the performance of targeted and non-targeted metabolomics and provides new insight into the advantages and disadvantages of each approach.
Topics: Algorithms; Animals; Brain; Chromatography, Liquid; Fish Proteins; Humans; Liver; Mass Spectrometry; Metabolome; Metabolomics; Sea Bream
PubMed: 30439966
DOI: 10.1371/journal.pone.0207082 -
Current Opinion in Chemical Biology Feb 2020Understanding the molecular mechanisms of endogenous and environmental metabolites is crucial for basic biology and drug discovery. With the genome, proteome, and... (Review)
Review
Understanding the molecular mechanisms of endogenous and environmental metabolites is crucial for basic biology and drug discovery. With the genome, proteome, and metabolome of many organisms being readily available, researchers now have the opportunity to dissect how key metabolites regulate complex cellular pathways in vivo. Nonetheless, characterizing the specific and functional protein targets of key metabolites associated with specific cellular phenotypes remains a major challenge. Innovations in chemical biology are now poised to address this fundamental limitation in physiology and disease. In this review, we highlight recent advances in chemoproteomics for targeted and proteome-wide analysis of metabolite-protein interactions that have enabled the discovery of unpredicted metabolite-protein interactions and facilitated the development of new small molecule therapeutics.
Topics: Humans; Metabolome; Metabolomics; Proteins; Proteome; Proteomics
PubMed: 31790852
DOI: 10.1016/j.cbpa.2019.10.008 -
Progress in Nuclear Magnetic Resonance... May 2017Metabolomics is undergoing tremendous growth and is being employed to solve a diversity of biological problems from environmental issues to the identification of... (Review)
Review
Metabolomics is undergoing tremendous growth and is being employed to solve a diversity of biological problems from environmental issues to the identification of biomarkers for human diseases. Nuclear magnetic resonance (NMR) and mass spectrometry (MS) are the analytical tools that are routinely, but separately, used to obtain metabolomics data sets due to their versatility, accessibility, and unique strengths. NMR requires minimal sample handling without the need for chromatography, is easily quantitative, and provides multiple means of metabolite identification, but is limited to detecting the most abundant metabolites (⩾1μM). Conversely, mass spectrometry has the ability to measure metabolites at very low concentrations (femtomolar to attomolar) and has a higher resolution (∼10-10) and dynamic range (∼10-10), but quantitation is a challenge and sample complexity may limit metabolite detection because of ion suppression. Consequently, liquid chromatography (LC) or gas chromatography (GC) is commonly employed in conjunction with MS, but this may lead to other sources of error. As a result, NMR and mass spectrometry are highly complementary, and combining the two techniques is likely to improve the overall quality of a study and enhance the coverage of the metabolome. While the majority of metabolomic studies use a single analytical source, there is a growing appreciation of the inherent value of combining NMR and MS for metabolomics. An overview of the current state of utilizing both NMR and MS for metabolomics will be presented.
Topics: Humans; Isotope Labeling; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolome; Metabolomics
PubMed: 28552170
DOI: 10.1016/j.pnmrs.2017.01.001 -
BioMed Research International 2013In the recent years, there has been an increase in the number of metabolomic approaches used, in parallel with proteomic and functional genomic studies. The wide variety... (Review)
Review
In the recent years, there has been an increase in the number of metabolomic approaches used, in parallel with proteomic and functional genomic studies. The wide variety of chemical types of metabolites available has also accelerated the use of different techniques in the investigation of the metabolome. At present, metabolomics is applied to investigate several human diseases, to improve their diagnosis and prevention, and to design better therapeutic strategies. In addition, metabolomic studies are also being carried out in areas such as toxicology and pharmacology, crop breeding, and plant biotechnology. In this review, we emphasize the use and application of metabolomics in human diseases and plant research to improve human health.
Topics: Biotechnology; Disease; Humans; Metabolome; Metabolomics; Plant Diseases; Plants
PubMed: 23986911
DOI: 10.1155/2013/792527 -
Circulation. Cardiovascular Genetics Apr 2017Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors... (Review)
Review
Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine--oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine.
Topics: American Heart Association; Cardiovascular Diseases; Humans; Metabolome; Metabolomics; Microbiota; United States
PubMed: 28360086
DOI: 10.1161/HCG.0000000000000032 -
International Journal of Molecular... Jun 2018A new era of plant biochemistry at the systems level is emerging, providing detailed descriptions of biochemical phenomena at the cellular and organismal level. This new... (Review)
Review
A new era of plant biochemistry at the systems level is emerging, providing detailed descriptions of biochemical phenomena at the cellular and organismal level. This new era is marked by the advent of metabolomics—the qualitative and quantitative investigation of the entire metabolome (in a dynamic equilibrium) of a biological system. This field has developed as an indispensable methodological approach to study cellular biochemistry at a global level. For protection and survival in a constantly-changing environment, plants rely on a complex and multi-layered innate immune system. This involves surveillance of ‘self’ and ‘non-self,’ molecule-based systemic signalling and metabolic adaptations involving primary and secondary metabolites as well as epigenetic modulation mechanisms. Establishment of a pre-conditioned or primed state can sensitise or enhance aspects of innate immunity for faster and stronger responses. Comprehensive elucidation of the molecular and biochemical processes associated with the phenotypic defence state is vital for a better understanding of the molecular mechanisms that define the metabolism of plant⁻pathogen interactions. Such insights are essential for translational research and applications. Thus, this review highlights the prospects of metabolomics and addresses current challenges that hinder the realisation of the full potential of the field. Such limitations include partial coverage of the metabolome and maximising the value of metabolomics data (extraction of information and interpretation). Furthermore, the review points out key features that characterise both the plant innate immune system and enhancement of the latter, thus underlining insights from metabolomic studies in plant priming. Future perspectives in this inspiring area are included, with the aim of stimulating further studies leading to a better understanding of plant immunity at the metabolome level.
Topics: Adaptation, Physiological; Crop Production; Epigenesis, Genetic; Metabolome; Metabolomics; Plant Immunity; Plant Physiological Phenomena; Plants
PubMed: 29899301
DOI: 10.3390/ijms19061759 -
Molecules (Basel, Switzerland) May 2024As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and... (Review)
Review
As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.
Topics: Metabolomics; Humans; Biomarkers; Mass Spectrometry; Drug Discovery; Metabolome; Animals
PubMed: 38792060
DOI: 10.3390/molecules29102198 -
Wiley Interdisciplinary Reviews.... 2015The human gut microbiota performs essential functions for host and well-being, but has also been linked to a variety of disease states, e.g., obesity and type 2... (Review)
Review
The human gut microbiota performs essential functions for host and well-being, but has also been linked to a variety of disease states, e.g., obesity and type 2 diabetes. The mammalian body fluid and tissue metabolomes are greatly influenced by the microbiota, with many health-relevant metabolites being considered 'mammalian-microbial co-metabolites'. To systematically investigate this complex host-microbial co-metabolism, a systems biology approach integrating high-throughput data and computational network models is required. Here, we review established top-down and bottom-up systems biology approaches that have successfully elucidated relationships between gut microbiota-derived metabolites and host health and disease. We focus particularly on the constraint-based modeling and analysis approach, which enables the prediction of mechanisms behind metabolic host-microbe interactions on the molecular level. We illustrate that constraint-based models are a useful tool for the contextualization of metabolomic measurements and can further our insight into host-microbe interactions, yielding, e.g., in potential novel drugs and biomarkers.
Topics: Animals; Body Fluids; Gastrointestinal Tract; Host-Pathogen Interactions; Humans; Metabolome; Metabolomics; Microbiota; Models, Biological
PubMed: 25929487
DOI: 10.1002/wsbm.1301