Perspective Of Metabolomics Research Articles

Gastric cancer: Metabolic and metabolomics perspectives (Review).

Gastric cancer is one of the most malignant tumors worldwide and remains a major health threat in Asia-Pacific regions, while its pathological mechanism is generally unknown. Recent research has advanced the understanding of the relationship between metabolic reprogramming and carcinogenesis. In particular, metabolic regulation and cancer research are being further brought into sharp focus with the emergence of metabolomics. Not only can metabolomics provide global information on metabolic profiles of specific tumors, but it can also act as a promising tool to discover biomarkers regarding diagnosis, metastatic surveillance and chemotherapeutic sensitivity prediction. Meanwhile, metabolism-based anticancer therapies will be further discovered. Up to now, accumulative studies have highlighted the application of metabolomics in gastric cancer research regarding different aspects; therefore we summarized the current available results of how metabolic changes are linked to gastric carcinogenesis, and how metabolomics holds promise for the diagnosis, metastatic surveillance, treatment and prognosis prediction of gastric cancer.

Comparative metabolomics analysis for the compatibility and incompatibility of kansui and licorice with different ratios by UHPLC-QTOF/MS and multivariate data analysis.

Kansui, the root of Euphorbia kansui T.N. Liou ex T.P. Wang (Euphorbiaceae), is a well-known poisonous traditional Chinese medicine (TCM). However, many monographs of TCM indicated that it cannot be co-used with licorice, as kansui-licorice is a typical "eighteen incompatible" medicaments. Our previous studies have indicated that kansui was effective in treating malignant pleural effusion (MPE), and the efficacy could be weakened by the co-use of licorice, even causing serious toxicity at the given ratio. Nevertheless, the actual mechanisms of their dosage-toxicity-efficacy relationship need to be well clarified. The present study aimed to investigate the effect of individual and combined use of kansui and licorice on MPE rats, and explain the underlying mechanisms from a metabolomic perspective. Urine samples were analyzed by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Partial least-squares discriminate analysis (PLS-DA) models were built to evaluate the interaction between kansui and licorice. Seven potential biomarkers contribute to the separation of model group and control group were tentatively identified. And selenoamino acid metabolism and nicotinate and nicotinamide metabolism with the impact-value 0.31 and 0.24, respectively, were filtered out as the most important metabolic pathways. Kansui and kansui-licorice at a ratio of 4:1 can treat MPE rats by adjusting abnormal metabolic pathways to the normal state, while it may have opposite result with kansui-licorice 1:4. The different influences to the two metabolic pathways may partially explain the dosage-toxicity-efficacy relationship of kansui-licorice with different ratios. The results could offer valuable insights into the compatibility property changes for the two herbs.

Energy metabolism and metabolomics response of Pacific white shrimp Litopenaeus vannamei to sulfide toxicity

The toxicity and poisoning mechanisms of sulfide were studied in Litopenaeus vannamei from the perspective of energy metabolism and metabolomics. The lethal concentrations of sulfide in L. vannamei (LC50) at 24h, 48h, 72h, and 96h were determined. Sulfide at a concentration of 0, 1/10 (425.5μg/L), and 1/5 (851μg/L) of the LC50 at 96h was used to test the metabolic responses of L. vannamei for 21days. The chronic exposure of shrimp to a higher sulfide concentration of 851μg/L decreased shrimp survival but did not affect weight gain or the hepatopancreas index. The glycogen content in the hepatopancreas and muscle and the activity of hepatopancreas cytochrome C oxidase of the shrimp exposed to all sulfide concentrations were significantly lower, and the serum glucose and lactic acid levels and lactic acid dehydrogenase activity were significantly lower than those in the control. Metabolomics assays showed that shrimp exposed to sulfide had lower amounts of serum pyruvic acid, succinic acid, glycine, alanine, and proline in the 425.5μg/L group and phosphate, succinic acid, beta-alanine, serine, and l-histidine in the 851μg/L group than in the control. Chronic sulfide exposure could disturb protein synthesis in shrimp but enhance gluconeogenesis and substrate absorption for ATP synthesis and tricarboxylic acid cycles to provide extra energy to cope with sulfide stress. Chronic sulfide exposure could adversely affect the health status of L. vannamei, as indicated by the high amounts of serum n-ethylmaleamic acid, pyroglutamic acid, aspartic acid and phenylalanine relative to the control. This study indicates that chronic exposure of shrimp to sulfide can decrease health and lower survival through functional changes in gluconeogenesis, protein synthesis and energy metabolism.

Multiplex Biomarker Approaches in Type 2 Diabetes Mellitus Research.

Type 2 diabetes mellitus is a multifactorial condition resulting in high fasting blood glucose levels. Although its diagnosis is straightforward, there is not one set of biomarkers or drug targets that can be used for classification or personalized treatment of individuals who suffer from this condition. Instead, the application of multiplex methods incorporating a systems biology approach is essential in order to increase our understanding of this disease. This chapter reviews the state of the art in biomarker studies of human type 2 diabetes from a proteomic and metabolomic perspective. Our main focus was on biomarkers for disease prediction as these could lead to early intervention strategies for the best possible patient outcomes.

Metabolome response to temperature-induced virulence gene expression in two genotypes of pathogenic Vibrio parahaemolyticus.

BackgroundVibrio parahaemolyticus is a main causative agent of serious human seafood-borne gastroenteritis disease. Many researchers have investigated its pathogenesis by observing the alteration of its virulence factors in different conditions. It was previously known that culture conditions will influence the gene expression and the metabolic profile of V. parahaemolyticus, but little attention has been paid on the relationship between them. In this study, for the first time, the metabolomics response in relation to the expression of two major virulence genes, tdh and trh, induced at three temperatures (4, 25 and 37 °C) was examined in two genotypes of pathogenic Vibrio parahaemolyticus (ATCC33846 (tdh+/trh−/tlh+) and ATCC17802 (tdh−/trh+/tlh+)).ResultsReverse transcription real-time PCR (RT-qPCR) analysis illustrated that the expression levels of tdh and trh induced at 25 °C in V. parahaemolyticus were significantly higher than those induced at 4 and 37 °C. Principal components analysis (PCA) based on the UPLC & Q-TOF MS data presented clearly distinct groups among the samples treated by different temperatures. Metabolic profiling demonstrated that 179 of 1,033 kinds of identified metabolites in ATCC33846 changed significantly (p <0.01) upon culturing at different temperatures, meanwhile 101 of 930 kinds of metabolites changed (p <0.01) in ATCC17802. Pearson’s correlation analysis highlighted the correlation between metabolites and virulence gene expression levels. At the threshold of | r | = 1, p <0.01, 12 kinds of metabolites showed extremely significant correlations with tdh expression, and 4 kinds of metabolites significantly correlated with trh expression. It is interesting that 3D, 7D, 11D-Phytanic acid showed the same trend with pyrophosphate, whose derivative could activate the degradation of phytanic acid. Several metabolites could be sorted into the same class by the method of chemical taxonomy, by assuming that they are involved in the same metabolic pathways.ConclusionsThis research can help to find biomarkers to monitor virulence gene expression, and can further help laboratory and clinical research of V. parahaemolyticus from the perspective of metabolomics.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0688-5) contains supplementary material, which is available to authorized users.

Urinary metabolite profiling provides potential differentiation to explore the mechanisms of adjuvant-induced arthritis in rats.

To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant-induced arthritis (AA). Sprague-Dawley rats were randomly divided into a control group and an experimental group, with eight in each. Rats in the experimental group were induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC-TOF/MS technology with multivariate statistical approaches, including principal component analysis, partial least squares discriminant analysis and orthogonal projections to latent structures-discriminant analysis. Nine potential biomarkers were identified, including 2,2-dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, l-dopa, 1,4-dihydroxy-2-naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. Copyright © 2016 John Wiley & Sons, Ltd.

Influence of the collection tube on metabolomic changes in serum and plasma

Major threats in metabolomics clinical research are biases in sampling and preparation of biological samples. Bias in sample collection is a frequently forgotten aspect responsible for uncontrolled errors in metabolomics analysis. There is a great diversity of blood collection tubes for sampling serum or plasma, which are widely used in metabolomics analysis. Most of the existing studies dealing with the influence of blood collection on metabolomics analysis have been restricted to comparison between plasma and serum. However, polymeric gel tubes, which are frequently proposed to accelerate the separation of serum and plasma, have not been studied. In the present research, samples of serum or plasma collected in polymeric gel tubes were compared with those taken in conventional tubes from a metabolomics perspective using an untargeted GC–TOF/MS approach. The main differences between serum and plasma collected in conventional tubes affected to critical pathways such as the citric acid cycle, metabolism of amino acids, fructose and mannose metabolism and that of glycerolipids, and pentose and glucuronate interconversion. On the other hand, the polymeric gel only promoted differences at the metabolite level in serum since no critical differences were observed between plasma collected with EDTA tubes and polymeric gel tubes. Thus, the main changes were attributable to serum collected in gel and affected to the metabolism of amino acids such as alanine, proline and threonine, the glycerolipids metabolism, and two primary metabolites such as aconitic acid and lactic acid. Therefore, these metabolite changes should be taken into account in planning an experimental protocol for metabolomics analysis.

Agronomic, metabolomic and lipidomic characterisation of Sicilian Origanum vulgare (L.) ecotypes

Although Origanum vulgare (L.) has been deeply analysed at phytochemical level, poor knowledge is available regarding non-volatile compounds such as lipids. The aim of this work was to characterise five wild Sicilian Origanum ecotypes from an agronomic, metabolomic and lipidomic perspective. Serradifalco presented higher dry weight and inflorescences/plant than the others while Favara had a significantly higher number of branches per plant and more extensive flowered stratum. Metabolomic analysis, performed with LC-MS-TOF, allowed a preliminary characterisation of the non-volatile metabolome of the five oregano ecotypes Origanum vulgare ssp. hirtum. Twenty-five metabolites were identified belonging to organic acids, amino acids, lysophosphatidylcholines, carnithines, nucleic bases and lysophosphatidylethanolamines. Lipidomic analysis identified 115 polar plant membrane glycerolipid species. Thirteen of them were differentially present in the two chosen ecotypes. The role of these metabolites in plant physiology from a qualitative and pharmacological point of view was discussed.

Salivary metabolomics in the diagnosis of oral cancer and periodontal diseases.

Metabolomics is a systemic study of metabolites, which are small molecules generated by the process of metabolism. The metabolic profile of saliva can provide an early outlook of the changes associated with a wide range of diseases, including oral cancer and periodontal diseases. It is possible to measure levels of disease-specific metabolites using different methods as presented in this study. However, many challenges exist including incomplete understanding of the complicated metabolic pathways of different oral diseases. The review concludes with the discussion on future perspectives of salivary metabolomics from a clinician point of view. Salivary metabolomics may afford a new research avenue to identify local and systemic disorders but also to aid in the design and modification of therapies. A MEDLINE search using keywords "salivary metabolomics" returned 23 results in total, of which seven were omitted for being reviews or letters to the editor. The rest of the articles were used for preparation of the review, 13 of these were published in the last 5years.

A metabolomic perspective of griseofulvin-induced liver injury in mice

Griseofulvin (GSF) causes hepatic porphyria in mice, which mimics the liver injury associated with erythropoietic protoporphyria (EPP) in humans. The current study investigated the biochemical basis of GSF-induced liver injury in mice using a metabolimic approach. GSF treatment in mice resulted in significant accumulations of protoporphyrin IX (PPIX), N-methyl PPIX, bile acids, and glutathione (GSH) in the liver. Metabolomic analysis also revealed bioactivation pathways of GSF that contributed to the formation of GSF-PPIX, GSF-GSH and GSF-proline adducts. GSF-PPIX is the precursor of N-methyl PPIX. A six-fold increase of N-methyl PPIX was observed in the liver of mice after GSF treatment. N-methyl PPIX strongly inhibits ferrochelatase, the enzyme that converts PPIX to heme, and leads to PPIX accumulation. Excessive PPIX in the liver results in bile duct blockage and disturbs bile acid homeostasis. The accumulation of GSH in the liver was likely due to Nrf2-mediated upregulation of GSH synthesis. In summary, this study provides the biochemical basis of GSF-induced liver injury that can be used to understand the pathophysiology of EPP-associated liver injury in humans.

Neglected diseases prioritized in Brazil under the perspective of metabolomics: A review.

This review article compiles in a critical manner literature publications regarding seven neglected diseases (ND) prioritized in Brazil (Chagas disease, dengue, leishmaniasis, leprosy, malaria, schistosomiasis, and tuberculosis) under the perspective of metabolomics. Both strategies, targeted and untargeted metabolomics, were considered in the compilation. The majority of studies focused on biomarker discovery for diagnostic purposes, and on the search of novel or alternative therapies against the ND under consideration, although temporal progression of the infection at metabolic level was also addressed. Tuberculosis, followed by schistosomiasis, malaria and leishmaniasis are the diseases that received larger attention in terms of number of publications. Dengue and leprosy were the least studied and Chagas disease received intermediate attention. NMR and HPLC-MS technologies continue to predominate among the analytical platforms of choice in the metabolomic studies of ND. A plethora of metabolites were identified in the compiled studies, with expressive predominancy of amino acids, organic acids, carbohydrates, nucleosides, lipids, fatty acids, and derivatives.

Perinatal asphyxia: a review from a metabolomics perspective.

Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most cases, infants successfully recover from hypoxia episodes; however, some patients may develop HIE, leading to permanent neurological conditions or impairment of different organs and systems. Given its multifactor dependency, the timing, severity and outcome of this disease, mainly assessed through Sarnat staging, are of difficult evaluation. Moreover, although the latest newborn resuscitation guideline suggests the use of a 21% oxygen concentration or room air, such an approach is still under debate. Therefore, the pathological mechanism is still not clear and a golden standard treatment has yet to be defined. In this context, metabolomics, a new discipline that has described important perinatal issues over the last years, proved to be a useful tool for the monitoring, the assessment, and the identification of potential biomarkers associated with asphyxia events. This review covers metabolomics research on perinatal asphyxia condition, examining in detail the studies reported both on animal and human models.

Metabolomics in chemical ecology.

Chemical ecology elucidates the nature and role of natural products as mediators of organismal interactions. The emerging techniques that can be summarized under the concept of metabolomics provide new opportunities to study such environmentally relevant signaling molecules. Especially comparative tools in metabolomics enable the identification of compounds that are regulated during interaction situations and that might play a role as e.g. pheromones, allelochemicals or in induced and activated defenses. This approach helps overcoming limitations of traditional bioassay-guided structure elucidation approaches. But the power of metabolomics is not limited to the comparison of metabolic profiles of interacting partners. Especially the link to other -omics techniques helps to unravel not only the compounds in question but the entire biosynthetic and genetic re-wiring, required for an ecological response. This review comprehensively highlights successful applications of metabolomics in chemical ecology and discusses existing limitations of these novel techniques. It focuses on recent developments in comparative metabolomics and discusses the use of metabolomics in the systems biology of organismal interactions. It also outlines the potential of large metabolomics initiatives for model organisms in the field of chemical ecology.

Metabolomics - the complementary field in systems biology: a review on obesity and type 2 diabetes.

Metabolomic studies on obesity and type 2 diabetes mellitus have led to a number of mechanistic insights into biomarker discovery and comprehension of disease progression at metabolic levels. This article reviews a series of metabolomic studies carried out in previous and recent years on obesity and type 2 diabetes, which have shown potential metabolic biomarkers for further evaluation of the diseases. Literature including journals and books from Web of Science, Pubmed and related databases reporting on the metabolomics in these particular disorders are reviewed. We herein discuss the potential of reported metabolic biomarkers for a novel understanding of disease processes. These biomarkers include fatty acids, TCA cycle intermediates, carbohydrates, amino acids, choline and bile acids. The biological activities and aetiological pathways of metabolites of interest in driving these intricate processes are explained. The data from various publications supported metabolomics as an effective strategy in the identification of novel biomarkers for obesity and type 2 diabetes. Accelerating interest in the perspective of metabolomics to complement other fields in systems biology towards the in-depth understanding of the molecular mechanisms underlying the diseases is also well appreciated. In conclusion, metabolomics can be used as one of the alternative approaches in biomarker discovery and the novel understanding of pathophysiological mechanisms in obesity and type 2 diabetes. It can be foreseen that there will be an increasing research interest to combine metabolomics with other omics platforms towards the establishment of detailed mechanistic evidence associated with the disease processes.

CD133-positive cancer stem cells from Colo205 human colon adenocarcinoma cell line show resistance to chemotherapy and display a specific metabolomic profile.

During the past decade, cancer stem-like cells (CSCs) have drawn substantial interest in cancer research since they have been described as major targets to improve treatment of tumors and to prevent recurrence and metastasis. In this paper, we report on the search for CSCs within the Colo205 human adenocarcinoma cell line. We describe that CD133 (prominin) was the only reliable marker for the isolation and characterization of CSCs within a Colo205 cell population. CD133-positive cells displayed many CSC characteristics, such as tumorsphere formation ability, expression of early-stage development markers, high invasiveness, raised tumor initiation potential and resistance to cisplatin chemotherapy treatment. In vitro analyses also highlighted a specific metabolomic profile of CD133-positive cells and we concluded that the chemotherapy resistance of CSCs could be related to the quiescence of such cells associated with their reduced metabolism. Furthermore, in vivo metabolome analyses suggested that a high level of circulating glutathione molecules could also promote treatment resistance. From the perspective of metabolomics, we also discuss the controversial use of serum-free in vitro cultures for CSC enrichment prior to further phenotype characterization.

Future Perspectives of Metabolomics in Adipocytes

Obesity and diabetes have reached global epidemic status in modern society. It is well known that metabolic syndrome leads to the progression of these diseases, eventually decreasing quality of life. In wake of these epidemics, adipose tissue has attracted significant attention because of its activity as an energy storage reservoir. Lately, even more importance has been given to the different classes of adipocytes including white, brown and beige adipose tissues. Most research has been focused on understanding molecular mechanisms of cellular signaling. However, not much is known about metabolic reprogramming and the influence of metabolic stimuli on adipocyte activity. Systems biology driven by untargeted metabolic profiling of adipocytes will bridge the gap between nutrition, metabolism and regulation of metabolic disorders. In particular, metabolomics, an emerging omic science, will play an important role in identifying biomarkers associated with these metabolic diseases. The aim of this review is to provide an overview of adipose tissue subclasses and their role in health and disease.

Staphylococcus aureus metabolic response to changing environmental conditions – A metabolomics perspective

Microorganisms preserve their metabolic function against a wide range of external perturbations including biotic or abiotic factors by utilizing cellular adaptations to maintain cell homeostasis. Functional genomics aims to detect such adaptive alterations on the level of transcriptome, proteome and metabolome to understand system wide changes and to identify interactions between the different levels of biochemical organization. Microbial metabolomics measures metabolites, the direct biochemical response to the environment, and is pivotal to the understanding of the variability and dynamics of bacterial cell metabolism. Metabolomics can measure many different types of compounds including primary metabolites, secondary metabolites, second messengers, quorum sensing compounds and others, which all contribute to the complex bacterial response to an environmental change. Recent data confirmed that many metabolic processes in pathogenic bacteria are linked to virulence and invasive capabilities. Deciphering bacterial metabolism in response to specific environmental conditions and in specific genetic backgrounds will help map the complex network between the metabolome and the other “-omes”. Here, we will review a selection of case studies for the pathogenic Gram-positive bacterium Staphylococcus aureus and summarize the current state of metabolomics literature covering staphylococci metabolism under different physiological states.

Metabolomics perspectives in pediatric research

Increasing evidence points toward the critical and long-term involvement of prenatal and early nutrition and lifestyle on later health and disease risk predisposition. Metabolomics is now a well-established top-down systems biology approach that explores the genetic-environment-health paradigm. The generalization of such approaches has opened new research areas to deepen our current understanding of many physiological processes, as well as foods and nutrient functionalities in target populations. It is envisioned that this will provide new avenues toward preventive medicine and prognostic strategies for tailored therapeutic and personalized nutrition management. The development of systems biology approaches and the new generation of biomarker patterns will provide the opportunity to associate complex metabolic regulations with the etiology of multifactorial pediatric diseases. This may subsequently lead to the development of system mechanistic hypotheses that could be targeted with new nutritional personalized concepts. Therefore, this review aims to describe recent applications of metabolomics in preclinical and clinical fields with insights into disease diagnostics/monitoring and improvement of homeostasis metabolic regulation that may be translatable to novel therapeutic and nutrition advances in pediatric research.

Advances in Ginkgo biloba research: Genomics and metabolomics perspectives

The maiden hair tree, Ginkgo biloba is very much resistant to a wide spectrum of biotic and abiotic stress conditions. It hardly seems to be attacked by any herbivore or microbe. In spite of its strong resistant nature to wide stress conditions, only little research has been carried out at genomics and metabolomics level to understand its mechanism of stress resistance. Ginkgolide and bilobalide, the unique terpene trilactone present in G. biloba were found to play an important role during stress conditions. Massive parallel sequencing of G. biloba leads to generation of 64057 expressed sequence tags (EST’s). Beside this, chloroplast genome (cpDNA) of G. biloba has been sequenced. This massive parallel sequencing of ESTs, along with cpDNA genome, will open the door for high throughput genomic research. Key words: Ginkgo biloba, cycad, ginkgolide, bilobalide, bilobol, proton nuclear magnetic resonance spectroscopy ( 1 H NMR).

Perspectives for metabolomics in testosterone replacement therapy

Testosterone is the major circulating androgen in men but exhibits an age-related decline in the ageing male. Late-onset hypogonadism or androgen deficiency syndrome (ADS) is a 'syndromic' disorder including both a persistent low testosterone serum concentration and major clinical symptoms, including erectile dysfunction, low libido, decreased muscle mass and strength, increased body fat, decreased vitality or depressed mood. Given its unspecific symptoms, treatment goals and monitoring parameters, this review will outline the various uncertainties concerning the diagnosis, therapy and monitoring of ADS to date. Literature was identified primarily through searches for specific investigators in the PubMed database. No date or language limits were applied in the literature search for the present review. The current state of research, showing that metabolomics is starting to have an impact not only on disease diagnosis and prognosis but also on drug treatment efficacy and safety monitoring, will be presented, and the application of metabolomics to improve the clinical management of ADS will be discussed. Finally, the scientific opportunities presented by metabolomics and other -omics as novel and promising tools for biomarker discovery and individualised testosterone replacement therapy in men will be explored.