PubMed

Plasma Metabolite Profiles in Response to Chronic Exercise. Med Sci Sports Exerc. 2018 Mar 05;: Authors: Brennan AM, Benson M, Morningstar J, Herzig M, Robbins J, Gerszten RE, Ross R Abstract PURPOSE: High throughput profiling of metabolic status (metabolomics) allows for the assessment of small-molecule metabolites that may participate in exercise-induced biochemical pathways and corresponding cardiometabolic risk modification. We sought to describe the changes in a diverse set of plasma metabolite profiles in patients undergoing chronic exercise training and assess the relationship between metabolites and cardiometabolic response to exercise. METHODS: A secondary analysis was performed in 216 middle-aged abdominally obese men and women ([mean (SD)], 52.4 (8.0) years) randomized into one of four groups varying in exercise amount and intensity for 6 months duration: high amount high intensity, high amount low intensity, low amount low intensity, and control. 147 metabolites were profiled by liquid chromatography-tandem mass spectrometry. RESULTS: No significant differences in metabolite changes between specific exercise groups were observed; therefore, subsequent analyses were collapsed across exercise groups. There were no significant differences in metabolite changes between the exercise and control groups after 24 weeks at a Bonferroni-adjusted statistical significance (p < 3.0 x 10). Seven metabolites changed in the exercise group compared to the control group at p < 0.05. Changes in several metabolites from distinct metabolic pathways were associated with change in cardiometabolic risk traits, and three baseline metabolite levels predicted changes in cardiometabolic risk traits. CONCLUSION: Metabolomic profiling revealed no significant plasma metabolite changes between exercise compared to control after 24-weeks at Bonferroni significance. However, we identified circulating biomarkers that were predictive or reflective of improvements in cardiometabolic traits in the exercise group. PMID: 29509640 [PubMed - as supplied by publisher]

Survival, gene and metabolite responses of Litoria verreauxii alpina frogs to fungal disease chytridiomycosis. Sci Data. 2018 Mar 06;5:180033 Authors: Grogan LF, Mulvenna J, Gummer JPA, Scheele BC, Berger L, Cashins SD, McFadden MS, Harlow P, Hunter DA, Trengove RD, Skerratt LF Abstract The fungal skin disease chytridiomycosis has caused the devastating decline and extinction of hundreds of amphibian species globally, yet the potential for evolving resistance, and the underlying pathophysiological mechanisms remain poorly understood. We exposed 406 naïve, captive-raised alpine tree frogs (Litoria verreauxii alpina) from multiple populations (one evolutionarily naïve to chytridiomycosis) to the aetiological agent Batrachochytrium dendrobatidis in two concurrent and controlled infection experiments. We investigated (A) survival outcomes and clinical pathogen burdens between populations and clutches, and (B) individual host tissue responses to chytridiomycosis. Here we present multiple interrelated datasets associated with these exposure experiments, including animal signalment, survival and pathogen burden of 355 animals from Experiment A, and the following datasets related to 61 animals from Experiment B: animal signalment and pathogen burden; raw RNA-Seq reads from skin, liver and spleen tissues; de novo assembled transcriptomes for each tissue type; raw gene expression data; annotation data for each gene; and raw metabolite expression data from skin and liver tissues. These data provide an extensive baseline for future analyses. PMID: 29509187 [PubMed - in process]

Related Articles H2 drives metabolic rearrangements in gas-fermenting Clostridium autoethanogenum. Biotechnol Biofuels. 2018;11:55 Authors: Valgepea K, de Souza Pinto Lemgruber R, Abdalla T, Binos S, Takemori N, Takemori A, Tanaka Y, Tappel R, Köpke M, Simpson SD, Nielsen LK, Marcellin E Abstract Background: The global demand for affordable carbon has never been stronger, and there is an imperative in many industrial processes to use waste streams to make products. Gas-fermenting acetogens offer a potential solution and several commercial gas fermentation plants are currently under construction. As energy limits acetogen metabolism, supply of H2 should diminish substrate loss to CO2 and facilitate production of reduced and energy-intensive products. However, the effects of H2 supply on CO-grown acetogens have yet to be experimentally quantified under controlled growth conditions. Results: Here, we quantify the effects of H2 supplementation by comparing growth on CO, syngas, and a high-H2 CO gas mix using chemostat cultures of Clostridium autoethanogenum. Cultures were characterised at the molecular level using metabolomics, proteomics, gas analysis, and a genome-scale metabolic model. CO-limited chemostats operated at two steady-state biomass concentrations facilitated co-utilisation of CO and H2. We show that H2 supply strongly impacts carbon distribution with a fourfold reduction in substrate loss as CO2 (61% vs. 17%) and a proportional increase of flux to ethanol (15% vs. 61%). Notably, H2 supplementation lowers the molar acetate/ethanol ratio by fivefold. At the molecular level, quantitative proteome analysis showed no obvious changes leading to these metabolic rearrangements suggesting the involvement of post-translational regulation. Metabolic modelling showed that H2 availability provided reducing power via H2 oxidation and saved redox as cells reduced all the CO2 to formate directly using H2 in the Wood-Ljungdahl pathway. Modelling further indicated that the methylene-THF reductase reaction was ferredoxin reducing under all conditions. In combination with proteomics, modelling also showed that ethanol was synthesised through the acetaldehyde:ferredoxin oxidoreductase (AOR) activity. Conclusions: Our quantitative molecular analysis revealed that H2 drives rearrangements at several layers of metabolism and provides novel links between carbon, energy, and redox metabolism advancing our understanding of energy conservation in acetogens. We conclude that H2 supply can substantially increase the efficiency of gas fermentation and thus the feed gas composition can be considered an important factor in developing gas fermentation-based bioprocesses. PMID: 29507607 [PubMed]

Related Articles Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach. Pharmacol Rev. 2018 Apr;70(2):348-383 Authors: Cuadrado A, Manda G, Hassan A, Alcaraz MJ, Barbas C, Daiber A, Ghezzi P, León R, López MG, Oliva B, Pajares M, Rojo AI, Robledinos-Antón N, Valverde AM, Guney E, Schmidt HHHW Abstract Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases. PMID: 29507103 [PubMed - in process]

Related Articles Metabolomic profiling of women with gestational diabetes mellitus and their offspring: Review of metabolomics studies. J Diabetes Complications. 2018 Jan 31;: Authors: Chen Q, Francis E, Hu G, Chen L Abstract BACKGROUND: Gestational diabetes mellitus (GDM) reflects an increased risk of developing type 2 diabetes (T2D) after pregnancy in women. Offspring born to mothers with GDM are at an elevated risk of obesity and T2D at a young age. Currently, there are lack of ways for identifying women in early pregnancy who are at risk of developing GDM. As a result, both mothers and fetus are not treated until late in the second trimester when GDM is diagnosed. The recent advance in metabolomics, a new approach of systematic investigation of the metabolites, provides an opportunity for early detection of GDM, and classifying the risk of subsequent chronic diseases among women and their offspring. METHODS: We reviewed the literatures published in the past 20 years on studies using high-throughput metabolomics technologies to investigate women with GDM and their offspring. CONCLUSIONS: Despite the inconsistent results, previous studies have identified biomarkers that involved in specific metabolite groups and several pathways, including amino acid metabolism, steroid hormone biosynthesis, glycerophospholipid metabolism, and fatty acid metabolism. However, most studies have small sample sizes. Further research is warranted to determine if metabolomics will result in new indicators for the diagnosis, management, and prognosis of GDM and related complications. PMID: 29506818 [PubMed - as supplied by publisher]

Related Articles IntLIM: integration using linear models of metabolomics and gene expression data. BMC Bioinformatics. 2018 Mar 05;19(1):81 Authors: Siddiqui JK, Baskin E, Liu M, Cantemir-Stone CZ, Zhang B, Bonneville R, McElroy JP, Coombes KR, Mathé EA Abstract BACKGROUND: Integration of transcriptomic and metabolomic data improves functional interpretation of disease-related metabolomic phenotypes, and facilitates discovery of putative metabolite biomarkers and gene targets. For this reason, these data are increasingly collected in large (> 100 participants) cohorts, thereby driving a need for the development of user-friendly and open-source methods/tools for their integration. Of note, clinical/translational studies typically provide snapshot (e.g. one time point) gene and metabolite profiles and, oftentimes, most metabolites measured are not identified. Thus, in these types of studies, pathway/network approaches that take into account the complexity of transcript-metabolite relationships may neither be applicable nor readily uncover novel relationships. With this in mind, we propose a simple linear modeling approach to capture disease-(or other phenotype) specific gene-metabolite associations, with the assumption that co-regulation patterns reflect functionally related genes and metabolites. RESULTS: The proposed linear model, metabolite ~ gene + phenotype + gene:phenotype, specifically evaluates whether gene-metabolite relationships differ by phenotype, by testing whether the relationship in one phenotype is significantly different from the relationship in another phenotype (via a statistical interaction gene:phenotype p-value). Statistical interaction p-values for all possible gene-metabolite pairs are computed and significant pairs are then clustered by the directionality of associations (e.g. strong positive association in one phenotype, strong negative association in another phenotype). We implemented our approach as an R package, IntLIM, which includes a user-friendly R Shiny web interface, thereby making the integrative analyses accessible to non-computational experts. We applied IntLIM to two previously published datasets, collected in the NCI-60 cancer cell lines and in human breast tumor and non-tumor tissue, for which transcriptomic and metabolomic data are available. We demonstrate that IntLIM captures relevant tumor-specific gene-metabolite associations involved in known cancer-related pathways, including glutamine metabolism. Using IntLIM, we also uncover biologically relevant novel relationships that could be further tested experimentally. CONCLUSIONS: IntLIM provides a user-friendly, reproducible framework to integrate transcriptomic and metabolomic data and help interpret metabolomic data and uncover novel gene-metabolite relationships. The IntLIM R package is publicly available in GitHub ( https://github.com/mathelab/IntLIM ) and includes a user-friendly web application, vignettes, sample data and data/code to reproduce results. PMID: 29506475 [PubMed - in process]

Related Articles The novel hypoxia-inducible factor-1α inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth. Cell Death Dis. 2017 Jun 01;8(6):e2843 Authors: Ban HS, Kim BK, Lee H, Kim HM, Harmalkar D, Nam M, Park SK, Lee K, Park JT, Kim I, Lee K, Hwang GS, Won M Abstract HIF-1 is associated with poor prognoses and therapeutic resistance in cancer patients. We previously developed a novel hypoxia-inducible factor (HIF)-1 inhibitor, IDF-11774, a clinical candidate for cancer therapy. We also reported that IDF-1174 inhibited HSP70 chaperone activity and suppressed accumulation of HIF-1α. In this study, IDF-11774 inhibited the accumulation of HIF-1α in vitro and in vivo in colorectal carcinoma HCT116 cells under hypoxic conditions. Moreover, IDF-11774 treatment suppressed angiogenesis of cancer cells by reducing the expression of HIF-1 target genes, reduced glucose uptake, thereby sensitizing cells to growth under low glucose conditions, and decreased the extracellular acidification rate (ECAR) and oxygen consumption rate of cancer cells. Metabolic profiling of IDF-11774-treated cells revealed low levels of NAD+, NADP+, and lactate, as well as of intermediates in glycolysis and the tricarboxylic acid cycle. In addition, we observed elevated AMP and diminished ATP levels, resulting in a high AMP/ATP ratio. The level of AMP-activated protein kinase phosphorylation also increased, leading to inhibition of mTOR signaling in treated cells. In vivo xenograft assays demonstrated that IDF-11774 exhibited substantial anticancer efficacy in mouse models containing KRAS, PTEN, or VHL mutations, which often occur in malignant cancers. Collectively, our data indicate that IDF-11774 suppressed hypoxia-induced HIF-1α accumulation and repressed tumor growth by targeting energy production-related cancer metabolism. PMID: 28569777 [PubMed - indexed for MEDLINE]

Related Articles Rapid discovery of absorbed constituents and metabolites in rat plasma after the oral administration of Zi Shen Wan using high-throughput UHPLC-MS with a multivariate analysis approach. J Sep Sci. 2016 Dec;39(24):4700-4711 Authors: Li XN, Zhang A, Sun H, Song Y, Zou D, Wang X Abstract Zi Shen Wan is a typical formula consisting of three herbs, Phellodendri Amurensis Cortex, Rhizoma Anemarrhenae, and Cortex Cinnamomi, and has been widely used for treating prostatitis and infection diseases. However, it lacks in-depth research of the constituents of Zi Shen Wan in vivo and in vitro. In this work, ultra high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and MassLynx software was established to characterize the chemical compositions of Zi Shen Wan in vivo and in vitro. In total, 92 peaks were characterized in vitro and 33 peaks were characterized in vivo based on mass spectrometry and tandem mass spectrometry data. Among the 33 compounds characterized in rat plasma, 22 prototype components absorbed in rat serum and 11 metabolites were identified in vivo. This work was fully reports the chemical constituents of traditional Chinese formula of Zi Shen Wan, it demonstrated that ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry coupled to MassLynx software and multivariate data processing approach could be successfully applied for rapid screening and comprehensive analysis of chemical constituents in vitro and prototype components or metabolites in vivo of traditional Chinese medicine. PMID: 27778479 [PubMed - indexed for MEDLINE]

Related Articles Nonfasting for Routine Lipid Testing: From Evidence to Action. JAMA Intern Med. 2016 07 01;176(7):1005-6 Authors: Mora S PMID: 27119719 [PubMed - indexed for MEDLINE]

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/03/06PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Comprehensive transcriptome analyses correlated with untargeted metabolome reveal differentially expressed pathways in response to cell wall alterations. Plant Mol Biol. 2018 Mar 03;: Authors: Reem NT, Chen HY, Hur M, Zhao X, Wurtele ES, Li X, Li L, Zabotina O Abstract KEY MESSAGE: This research provides new insights into plant response to cell wall perturbations through correlation of transcriptome and metabolome datasets obtained from transgenic plants expressing cell wall-modifying enzymes. Plants respond to changes in their cell walls in order to protect themselves from pathogens and other stresses. Cell wall modifications in Arabidopsis thaliana have profound effects on gene expression and defense response, but the cell signaling mechanisms underlying these responses are not well understood. Three transgenic Arabidopsis lines, two with reduced cell wall acetylation (AnAXE and AnRAE) and one with reduced feruloylation (AnFAE), were used in this study to investigate the plant responses to cell wall modifications. RNA-Seq in combination with untargeted metabolome was employed to assess differential gene expression and metabolite abundance. RNA-Seq results were correlated with metabolite abundances to determine the pathways involved in response to cell wall modifications introduced in each line. The resulting pathway enrichments revealed the deacetylation events in AnAXE and AnRAE plants induced similar responses, notably, upregulation of aromatic amino acid biosynthesis and changes in regulation of primary metabolic pathways that supply substrates to specialized metabolism, particularly those related to defense responses. In contrast, genes and metabolites of lipid biosynthetic pathways and peroxidases involved in lignin polymerization were downregulated in AnFAE plants. These results elucidate how primary metabolism responds to extracellular stimuli. Combining the transcriptomics and metabolomics datasets increased the power of pathway prediction, and demonstrated the complexity of pathways involved in cell wall-mediated signaling. PMID: 29502299 [PubMed - as supplied by publisher]

The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans. Glycoconj J. 2018 Mar 03;: Authors: Link-Lenczowski P, Bubka M, Balog CIA, Koeleman CAM, Butters TD, Wuhrer M, Lityńska A Abstract N-acetylglucosaminyltransferase III (GnT-III) is known to catalyze N-glycan "bisection" and thereby modulate the formation of highly branched complex structures within the Golgi apparatus. While active, it inhibits the action of other GlcNAc transferases such as GnT-IV and GnT-V. Moreover, GnT-III is considered as an inhibitor of the metastatic potential of cancer cells both in vitro and in vivo. However, the effects of GnT-III may be more diverse and depend on the cellular context. We describe the detailed glycomic analysis of the effect of GnT-III overexpression in WM266-4-GnT-III metastatic melanoma cells. We used MALDI-TOF and ESI-ion-trap-MS/MS together with HILIC-HPLC of 2-AA labeled N-glycans to study the N-glycome of membrane-attached and secreted proteins. We found that the overexpression of GnT-III in melanoma leads to the modification of a broad range of N-glycan types by the introduction of the "bisecting" GlcNAc residue with highly branched complex structures among them. The presence of these unusual complex N-glycans resulted in stronger interactions of cellular glycoproteins with the PHA-L. Based on the data presented here we conclude that elevated activity of GnT-III in cancer cells does not necessarily lead to a total abrogation of the formation of highly branched glycans. In addition, the modification of pre-existing N-glycans by the introduction of "bisecting" GlcNAc can modulate their capacity to interact with carbohydrate-binding proteins such as plant lectins. Our results suggest further studies on the biological function of "bisected" oligosaccharides in cancer cell biology and their interactions with carbohydrate-binding proteins. PMID: 29502191 [PubMed - as supplied by publisher]

[Changes of cerebral cortical metabolomics in rats following benzo[a]pyrene exposure]. Nan Fang Yi Ke Da Xue Xue Bao. 2018 Feb 20;38(2):162-167 Authors: Wang J, Li CL, Bai LL, Tang QH, Zhang RY, Han TL, Guo YM, N Baker P, Xia YY, Tu BJ Abstract OBJECTIVE: To analyze the changes in endogenous small molecule metabolites after benzo[a]pyrene (B[a]P) exposure in rat cerebral cortex and explore the mechanism of B[a]P neurotoxicity. METHODS: Five-day-old SD rats were subjected to gavage administration of 2 mg/kg B[a]P for 7 consecutive weeks. After the exposure, the rats were assessed for spatial learning ability using Morris water maze test, ultrastructural changes of the cortical neurons under electron microscope, and metabolite profiles of the cortex using GC/MS. The differential metabolites between the exposed and control rats were identified with partial least squares discriminant analysis (PLS-DA) and the metabolic pathways related with the differential metabolites were analyzed using Cytoscape software. RESULTS: Compared with the control group, the rats exposed to B[a]P showed significantly increased escape latency (P<0.05) and decreased time spent in the target area (P<0.05). The exposed rats exhibited widened synaptic cleft, thickened endplate membrane and swollen cytoplasm compared with the control rats. Eighteen differential metabolites (VIP>1, P<0.05) in the cortex were identified between the two groups, and 9 pathways associated with B[a]P neurotoxicity were identified involving amino acid metabolism, tricarboxylic acid cycle and Vitamin B3 (niacin and nicotinamide) metabolism. CONCLUSION: B[a]P can cause disturbance in normal metabolisms and its neurotoxicity is possibly related with disorders in amino acid metabolism, tricarboxylic acid cycle and vitamin metabolism. PMID: 29502054 [PubMed - in process]

UPLC-G2Si-HDMS untargeted metabolomics for identification of metabolic targets of Yin-Chen-Hao-Tang used as a therapeutic agent of dampness-heat jaundice syndrome. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Feb 27;1081-1082:41-50 Authors: Sun H, Yang L, Li MX, Fang H, Zhang AH, Song Q, Liu XY, Su J, Yu MD, Makino T, Wang XJ Abstract Yin-Chen-Hao-Tang (YCHT), the classic formulae of traditional Chinese medicine (TCM), is widely used to treat dampness-heat jaundice syndrome (DHJS) and various liver diseases. However, the therapeutic mechanism of YCHT is yet to have an integrated biological interpretation. In this work, we used metabolomics technology to reveal the adjustment of small molecule metabolites in body during the treatment of YCHT. Aim to discover the serum biomarkers which are associated with the treatment of DHJS against YCHT. Pathological results and biochemical indicators showed that the hepatic injury and liver index abnormalities caused by DHJS was effectively improve after treatment with YCHT. On the basis of effective treatment, ultra-high performance liquid chromatography (UPLC-G2Si-HDMS) combined with the multivariate statistical analysis method was utilized to analyze the serum samples. Finally, 22 biomarkers were identified by using mass spectrometry and illuminated the correlative metabolic pathways which play a significant role and as therapeutic targets in the treatment of DHJS. This work demonstrated that mass spectrometry metabolomics provides a new insight to elucidate the action mechanism of formulae. PMID: 29502028 [PubMed - as supplied by publisher]

Multiple nucleobase transporters contribute to boscalid sensitivity in Aspergillus nidulans. Fungal Genet Biol. 2018 Feb 28;: Authors: Kalampokis IF, Kapetanakis GC, Aliferis KA, Diallinas G Abstract The development of fungicide-resistant fungal populations represents a major challenge for the agrochemical and agri-food sectors, which threatens food supply and security. The issue becomes complex for fungi that cause quantitative and qualitative losses due to mycotoxin biosynthesis. Nonetheless, currently, the molecular details underlying fungicide action and fungal resistance mechanisms are partially known. Here, we have investigated whether plasma membrane transporters contribute to specific fungicide uptake in the model fungus Aspergillus nidulans. Independent physiological tests and toxicity screening of selected fungicides provided evidence that the antifungal activity of Succinate Dehydrogenase Inhibitors (SDHIs) is associated with the expression of several nucleobase-related transporters. In particular, it was shown that a strain genetically inactivated in all seven nucleobase-related transporters is resistant to the fungicide boscalid, whereas none of the single null mutants exhibited significant resistance level. By constructing and testing isogenic strains that over-express each one of the seven transporters, we confirmed that five of them, namely, UapC, AzgA, FycB, CntA, and FurA, contribute to boscalid uptake. Additionally, by employing metabolomics we have examined the effect of boscalid on the metabolism of isogenic strains expressing or genetically lacking boscalid-related nucleobase transporters. The results confirmed the involvement of specific nucleobase transporters in fungicide uptake, leading to the discovery of corresponding metabolites-biomarkers. This work is the first report on the involvement of specific transporters in fungicide uptake and toxicity and their impact on fungal metabolism regulation and results might be further exploited towards the deeper understanding of fungal resistance to fungicides. PMID: 29501616 [PubMed - as supplied by publisher]

A review of nanoscale LC-ESI for metabolomics and its potential to enhance the metabolome coverage. Talanta. 2018 May 15;182:380-390 Authors: Chetwynd AJ, David A Abstract Liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) platforms are widely used to perform high throughput untargeted profiling of biological samples for metabolomics-based approaches. However, these LC-ESI platforms usually favour the detection of metabolites present at relatively high concentrations because of analytical limitations such as ion suppression, thus reducing overall sensitivity. To counter this issue of sensitivity, the latest in terms of analytical platforms can be adopted to enable a greater portion of the metabolome to be analysed in a single analytical run. Here, nanoflow liquid chromatography-nanoelectrospray ionisation (nLC-nESI), which has previously been utilised successfully in proteomics, is explored for use in metabolomic and exposomic research. As a discovery based field, the markedly increased sensitivity of these nLC-nESI platforms offer the potential to uncover the roles played by low abundant signalling metabolites (e.g. steroids, eicosanoids) in health and disease studies, and would also enable an improvement in the detection of xenobiotics present at trace levels in biological matrices to better characterise the chemical exposome. This review aims to give an insight into the advantages associated with nLC-nESI for metabolomics-based approaches. Initially we detail the source of improved sensitivity prior to reviewing the available approaches to achieving nanoflow rates and nanospray ionisation for metabolomics. The robustness of nLC-nESI platforms was then assessed using the literature available from a metabolomic viewpoint. We also discuss the challenging point of sample preparation which needs to be addressed to fully enjoy the benefits of these nLC-nESI platforms. Finally, we assess metabolomic analysis utilising nano scale platforms and look ahead to the future of metabolomics using these new highly sensitive platforms. PMID: 29501168 [PubMed - in process]

Alcohol and substance use are associated with altered metabolome in the first trimester serum samples of pregnant mothers. Eur J Obstet Gynecol Reprod Biol. 2018 Feb 17;223:79-84 Authors: Lehikoinen AI, Kärkkäinen OK, Lehtonen MAS, Auriola SOK, Hanhineva KJ, Heinonen ST Abstract BACKGROUND: Although the effects of alcohol on metabolic processes in the body have been studied widely, there do not appear to be any previous reports clarifying how substance abuse changes metabolic profiles of pregnant women during the first trimester of pregnancy. OBJECTIVE: Our aim was to evaluate the effect of substance abuse, especially alcohol use, on the metabolic profile of pregnant women during the first trimester. STUDY DESIGN: We applied mass spectrometry based non-targeted metabolite profiling of serum collected during routine visit to the hospital between gestational weeks 9 + 0 to 11 + 6 from controls (n = 55), alcohol users (n = 19), drug users (n = 24) and tobacco smokers (n = 40). RESULTS: We observed statistically significantly differences among the study groups in serum levels of glutamate, glutamine, and serotonin (p-values ≤ 0.0001). The serum levels of glutamate were increased in alcohol and drug using mothers when compared to the controls, whereas levels of glutamine were decreased in alcohol and drug using mothers. In addition, serum levels of serotonin were decreased in alcohol using mothers when compared to the controls. CONCLUSION: The present study shows that alcohol and drug use were associated with increased glutamate, and decreased glutamine levels, and alcohol use is associated with decreased serotonin levels. This study serves as a proof-of-concept that the metabolite profile of human first trimester serum samples could be used to detect alcohol exposure during pregnancy. PMID: 29500949 [PubMed - as supplied by publisher]

Alterations in Gut Microbial Function Following Liver Transplant. Liver Transpl. 2018 Mar 03;: Authors: Bajaj JS, Kakiyama G, Cox IJ, Nittono H, Takei H, White M, Fagan A, Gavis EA, Heuman DM, Gilles HC, Hylemon P, Taylor-Robinson SD, Legido-Quigley C, Kim M, Xu J, Williams R, Sikaroodi M, Pandak WM, Gillevet PM Abstract Liver transplant (LT) improves daily function and ameliorates gut microbial composition. However, the effect of LT on microbial functionality, which can be related to overall patient benefit, is unclear and could affect the post-LT course. AIMS: To determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism and lipidomics. METHOD: We enrolled outpatient cirrhotic patients on the LT list and followed them till 6 months post-LT. Microbiota composition (Shannon diversity and individual taxa) and function analysis (serum endotoxin, urinary metabolomics and serum lipidomics, and stool BA profile) and cognitive tests were performed at both visits. RESULTS: We enrolled 40 patients (56±7 years, MELD 23). They received LT 6±3 months after enrollment and were re-evaluated 7±3 months post-LT with a stable course. A significant improvement in cognition with increase in microbial diversity, increase in autochthonous and decrease in potentially pathogenic taxa and reduced endotoxemia were seen post-LT compared to baseline. Stool BAs increased significantly post-LT and there was evidence of greater bacterial action (higher secondary, oxo and iso-BAs) post-LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine (PAG) post-LT. There was an increase in urinary trimethylamine-N-oxide (TMAO), which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post-LT lipidomic profile appeared beneficial compared to the pre-LT. CONCLUSIONS: LT improves gut microbiota diversity and dysbiosis which is accompanied by favorable changes in gut microbial functionality corresponding to bile acids, ammonia, endotoxemia, lipidomic and metabolomic profiles. This article is protected by copyright. All rights reserved. PMID: 29500907 [PubMed - as supplied by publisher]

Metabolomics profiles of hepatocellular carcinoma in a Korean prospective cohort: the Korean Cancer Prevention Study-II. Cancer Prev Res (Phila). 2018 Mar 02;: Authors: Jee SH, Kim M, Kim M, Yoo HJ, Kim H, Jung KJ, Hong S, Lee JH Abstract In the prospective Korean Cancer Prevention Study-II (KCPS-II), we investigated the application of metabolomics to differentiate subjects with incident hepatocellular carcinoma (HCC group) from subjects who remained free of cancer (control group) during a mean follow-up period of 7 years with the aim of identifying valuable metabolic biomarkers for HCC. We used baseline serum samples from 75 subjects with incident HCC and 134 age- and gender-matched cancer-free subjects. Serum metabolic profiles associated with HCC incidence were investigated via metabolomics analysis. Compared to the control group, the HCC group showed significantly higher serum levels of aspartate aminotransferase (AST), alanine aminotransferase, and gamma-glutamyl transpeptidase. At baseline, compared to the control group, the HCC group showed significantly higher levels of 9 metabolites, including leucine, 5-hydroxyhexanoic acid, phenylalanine, tyrosine, arachidonic acid, and tauroursodeoxycholic acid (TUDCA), but lower levels of 28 metabolites, including oleamide, androsterone sulfate, L-palmitoylcarnitine, lysophosphatidic acid (LPA) 16:0, LPA 18:1, and lysophosphatidylcholines (lysoPCs). Multiple linear regression revealed that the incidence of HCC was associated with the levels of tyrosine, AST, lysoPCs (16:1, 20:3), oleamide, 5-hydroxyhexanoic acid, androsterone sulfate, and TUDCA (adjusted R2=0.514, P=0.036). This study showed the clinical relevance of the dysregulation of not only branched amino acids, aromatic amino acids, and lysoPCs but also bile acid biosynthesis and linoleic acid, arachidonic acid and fatty acid metabolism. Additionally, tyrosine, AST, lysoPCs (16:1, 20:3), oleamide, 5-hydroxyhexanoic acid, androsterone sulfate, and TUDCA were identified as independent variables associated with the incidence of HCC. PMID: 29500188 [PubMed - as supplied by publisher]

Development of an analytical method for polycyclic aromatic hydrocarbons in coffee beverages and dark beer using novel high-sensitivity technique of supercritical fluid chromatography/mass spectrometry. J Biosci Bioeng. 2018 Feb 28;: Authors: Yoshioka T, Nagatomi Y, Harayama K, Bamba T Abstract Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic substances that are mainly generated during heating in food; therefore, the European Union (EU) has regulated the amount of benzo[a]pyrene and PAH4 in various types of food. In addition, the Scientific Committee on Food of the EU and the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives have recommended that 16 PAHs should be monitored. Since coffee beverages and dark beer are roasted during manufacture, monitoring these 16 PAHs is of great importance. On the other hand, supercritical fluid chromatography (SFC) is a separation method that has garnered attention in recent years as a complement for liquid and gas chromatography. Therefore, we developed a rapid high-sensitivity analytical method for the above-mentioned 16 PAHs in coffee beverages and dark beer involving supercritical fluid chromatography/atmospheric pressure chemical ionization-mass spectrometry (SFC/APCI-MS) and simple sample preparation. In this study, we developed a novel analytical technique that increased the sensitivity of MS detection by varying the back-pressure in SFC depending on the elution of PAHs. In addition, analysis of commercially available coffee and dark beer samples in Japan showed that the risk of containing the 16 PAHs may be low. PMID: 29499993 [PubMed - as supplied by publisher]