PubMed

Related Articles Analysis of short-term metabolic alterations in Arabidopsis following changes in the prevailing environmental conditions. Mol Plant. 2014 May;7(5):893-911 Authors: Florian A, Nikoloski Z, Sulpice R, Timm S, Araújo WL, Tohge T, Bauwe H, Fernie AR Abstract Although a considerable increase in our knowledge concerning the importance of metabolic adjustments to unfavorable growth conditions has been recently provided, relatively little is known about the adjustments which occur in response to fluctuation in environmental factors. Evaluating the metabolic adjustments occurring under changing environmental conditions thus offers a good opportunity to increase our current understanding of the crosstalk between the major pathways which are affected by such conditions. To this end, plants growing under normal conditions were transferred to different light and temperature conditions which were anticipated to affect (amongst other processes) the rates of photosynthesis and photorespiration and characterized at the physiological, molecular, and metabolic levels following this transition. Our results revealed similar behavior in response to both treatments and imply a tight connectivity of photorespiration with the major pathways of plant metabolism. They further highlight that the majority of the regulation of these pathways is not mediated at the level of transcription but that leaf metabolism is rather pre-poised to adapt to changes in these input parameters. PMID: 24503159 [PubMed - indexed for MEDLINE]

Hydroxycarboxylic acid receptors are essential for breast cancer cells to control their lipid/fatty acid metabolism. Oncotarget. 2015 Mar 14; Authors: Stäubert C, Broom OJ, Nordström A Abstract Cancer cells exhibit characteristic changes in their metabolism with efforts being made to address them therapeutically. However, targeting metabolic enzymes as such is a major challenge due to their essentiality for normal proliferating cells. The most successful pharmaceutical targets are G protein-coupled receptors (GPCRs), with more than 40% of all currently available drugs acting through them. We show that, a family of metabolite-sensing GPCRs, the Hydroxycarboxylic acid receptor family (HCAs), is crucial for breast cancer cells to control their metabolism and proliferation. We found HCA1 and HCA3 mRNA expression were significantly increased in breast cancer patient samples and detectable in primary human breast cancer patient cells. Furthermore, siRNA mediated knock-down of HCA3 induced considerable breast cancer cell death as did knock-down of HCA1, although to a lesser extent. Liquid Chromatography Mass Spectrometry based analyses of breast cancer cell medium revealed a role for HCA3 in controlling intracellular lipid/fatty acid metabolism. The presence of etomoxir or perhexiline, both inhibitors of fatty acid β-oxidation rescues breast cancer cells with knocked-down HCA3 from cell death. Our data encourages the development of drugs acting on cancer-specific metabolite-sensing GPCRs as novel anti-proliferative agents for cancer therapy. PMID: 25839160 [PubMed - as supplied by publisher]

Integrating -omics: systems biology as explored through C. elegans research. J Mol Biol. 2015 Mar 31; Authors: Van Assche R, Broeckx V, Boonen K, Maes E, De Haes W, Schoofs L, Temmerman L Abstract -Omics data have become indispensable to systems biology, which aims to describe the full complexity of functional cells, tissues, organs and organisms. Generating vast amounts of data via such methods, researchers have invested in ways of handling and interpreting these. From the large volumes of -omics data that have been gathered over the years, it is clear that the information derived from one -ome is usually far from complete. Now, individual techniques and methods for integration are maturing to the point that researchers can focus on network-based integration, rather than simply interpreting single-ome studies. This review evaluates the application of integrated -omics approaches with a focus on C. elegans studies, intending to direct researchers in this field to useful databases and inspiring examples. PMID: 25839106 [PubMed - as supplied by publisher]

cCMP and cUMP occur in vivo. Biochem Biophys Res Commun. 2015 Mar 30; Authors: Bähre H, Hartwig C, Munder A, Wolter S, Stelzer T, Schirmer B, Beckert U, Frank DW, Tümmler B, Kaever V, Seifert R Abstract Mammalian cells contain the cyclic pyrimidine nucleotides cCMP and cUMP. It is unknown whether these tentative new second messenger molecules occur in vivo. We used high performance liquid chromatography quadrupole tandem mass spectrometry to quantitate nucleoside 3´,5´-cyclic monophosphates. cCMP was detected in all organs studied, most notably pancreas, spleen and the female reproductive system. cUMP was not detected in organs, probably due to the intrinsically low sensitivity of mass spectrometry to detect this molecule and organ matrix effects. Intratracheal infection of mice with recombinant Pseudomonas aeruginosa harboring the nucleotidyl cyclase toxin ExoY massively increased cUMP in lung. The identity of cCMP and cUMP in organs was confirmed by high performance liquid chromatography quadrupole time of flight mass spectrometry. cUMP also appeared in serum, urine and faeces following infection. Taken together, this report unequivocally shows for the first time that cCMP and cUMP occur in vivo. PMID: 25838203 [PubMed - as supplied by publisher]

RNAi-based biosynthetic pathway screens to identify in vivo functions of non-nucleic acid-based metabolites such as lipids. Nat Protoc. 2015 May;10(5):681-700 Authors: Zhang H, Abraham N, Khan LA, Gobel V Abstract The field of metabolomics continues to catalog new compounds, but their functional analysis remains technically challenging, and roles beyond metabolism are largely unknown. Unbiased genetic/RNAi screens are powerful tools to identify the in vivo functions of protein-encoding genes, but not of nonproteinaceous compounds such as lipids. They can, however, identify the biosynthetic enzymes of these compounds-findings that are usually dismissed, as these typically synthesize multiple products. Here, we provide a method using follow-on biosynthetic pathway screens to identify the endpoint biosynthetic enzyme and thus the compound through which they act. The approach is based on the principle that all subsequently identified downstream biosynthetic enzymes contribute to the synthesis of at least this one end product. We describe how to systematically target lipid biosynthetic pathways; optimize targeting conditions; take advantage of pathway branchpoints; and validate results by genetic assays and biochemical analyses. This approach extends the power of unbiased genetic/RNAi screens to identify in vivo functions of non-nucleic acid-based metabolites beyond their metabolic roles. It will typically require several months to identify a metabolic end product by biosynthetic pathway screens, but this time will vary widely depending, among other factors, on the end product's location in the pathway, which determines the number of screens required for its identification. PMID: 25837419 [PubMed - in process]

The human NAD metabolome: Functions, metabolism and compartmentalization. Crit Rev Biochem Mol Biol. 2015 Apr 2;:1-14 Authors: Nikiforov A, Kulikova V, Ziegler M Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD(+) and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID: 25837229 [PubMed - as supplied by publisher]

Transgenic mice and metabolomics for study of hepatic xenobiotic metabolism and toxicity. Expert Opin Drug Metab Toxicol. 2015 Apr 2;:1-13 Authors: Gonzalez FJ, Fang ZZ, Ma X Abstract INTRODUCTION: The study of xenobiotic metabolism and toxicity has been greatly aided by the use of genetically modified mouse models and metabolomics. Areas covered: Gene knockout mice can be used to determine the enzymes responsible for the metabolism of xenobiotics in vivo and to examine the mechanisms of xenobiotic-induced toxicity. Humanized mouse models are especially important because there exist marked species differences in the xenobiotic-metabolizing enzymes and the nuclear receptors that regulate these enzymes. Humanized mice expressing CYPs and nuclear receptors including the pregnane X receptor, the major regulator of xenobiotic metabolism and transport were produced. With genetically modified mouse models, metabolomics can determine the metabolic map of many xenobiotics with a level of sensitivity that allows the discovery of even minor metabolites. This technology can be used for determining the mechanism of xenobiotic toxicity and to find early biomarkers for toxicity. Expert opinion: Metabolomics and genetically modified mouse models can be used for the study of xenobiotic metabolism and toxicity by: i) comparison of the metabolomics profiles between wild-type and genetically modified mice, and searching for genotype-dependent endogenous metabolites; ii) searching for and elucidating metabolites derived from xenobiotics; and iii) discovery of specific alterations of endogenous compounds induced by xenobiotics-induced toxicity. PMID: 25836352 [PubMed - as supplied by publisher]

Opisthorchiasis: An Overlooked Danger. PLoS Negl Trop Dis. 2015 Apr;9(4):e0003563 Authors: Ogorodova LM, Fedorova OS, Sripa B, Mordvinov VA, Katokhin AV, Keiser J, Odermatt P, Brindley PJ, Mayboroda OA, Velavan TP, Freidin MB, Sazonov AE, Saltykova IV, Pakharukova MY, Kovshirina YV, Kaloulis K, Krylova OY, Yazdanbakhsh M, TOPIC Consortium PMID: 25836334 [PubMed - as supplied by publisher]

Metabolic Modifications in Human Biofluids Suggest the Involvement of Sphingolipid, Antioxidant, and Glutamate Metabolism in Alzheimer's Disease Pathogenesis. J Alzheimers Dis. 2015 Apr 2; Authors: Ellis B, Hye A, Snowden SG Abstract Alzheimer's disease (AD) is the most common neurodegenerative dementia, with the accumulation of extracellular amyloid-β and formation of neurofibrillary tau tangles as leading explanations of pathology. With the difficulties of studying the brain directly, it is hoped that identifying the effect of AD on the metabolite composition of biofluids will provide insights into underlying mechanisms of pathology. The present review identified 705 distinct metabolite reports representing 448 structurally distinct metabolites in six human biofluids, with 147 metabolites increased and 214 metabolites decreased with AD, while 80 metabolites showed inconsistent shifts. Sphingolipid, antioxidant, and glutamate metabolism were found to be strongly associated with AD and were selected for detailed investigation of their role in pathogenesis. In plasma, two ceramides increased and eight sphingomyelins decreased with AD, with total ceramides shown to increase in both serum and cerebrospinal fluid. In general antioxidants were shown to be depleted, with oxidative stress markers elevated in a range of biofluids in patients suggesting AD produces a pro-oxidative environment. Shifts in glutamate and glutamine and elevation of 4-hydroxy-2-nonenal suggests peroxidation of the astrocyte lipid bilayer resulting in reduced glutamate clearance from the synaptic cleft, suggesting a excitotoxicity component to AD pathology; however, due to inconsistencies in literature reports, reliable interpretation is difficult. The present review has shown that metabolite shifts in biofluids can provide valuable insights into potential pathological mechanisms in the brain, with sphingolipid, antioxidant, and glutamate metabolism being implicated in AD pathology. PMID: 25835424 [PubMed - as supplied by publisher]

Autism spectrum disorders and intestinal microbiota. Gut Microbes. 2015 Apr 2;:0 Authors: De Angelis M, Francavilla R, Piccolo M, De Giacomo A, Gobbetti M Abstract Through extensive microbial-mammalian co-metabolism, the intestinal microbiota have evolved to exert a marked influence on health and disease via gut-brain-microbiota interactions. In this addendum, we summarize the findings of our recent study on the fecal microbiota and metabolomes of children with pervasive developmental disorder-not otherwise specified (PDD-NOS) or autism (AD) compared with healthy children (HC). Children with PDD-NOS or AD have altered fecal microbiota and metabolomes (including neurotransmitter molecules). We hypothesise that the degree of microbial alteration correlates with the severity of the disease since fecal microbiota and metabolomes alterations were higher in children with PDD-NOS and, especially, AD compared to HC. Our study indicates that the levels of free amino acids (FAA) and volatile organic compounds (VOC) differ in AD subjects compared to children with PDD-NOS, who are more similar to HC. Finally, we propose a new perspective on the implications for the interaction between intestinal microbiota and AD. PMID: 25835343 [PubMed - as supplied by publisher]

Metabolomic Analysis of Clinical Plasma from Cerebral Infarction Patients Presenting with Blood Stasis. Evid Based Complement Alternat Med. 2015;2015:453423 Authors: Cha MH, Kim MJ, Jung J, Kim JH, Lee MS, Kim MS Abstract Blood stasis (BS) is characterized as a disorder of blood circulation. In traditional Korean medicine (TKM), it is viewed as a cause factor of diseases such as multiple sclerosis and stroke. This study investigated differences in the plasma metabolites profiles of subjects displaying BS or non-BS patterns. Thirty-one patients with cerebral infarction diagnosed with BS and an equal number of sex- and age-matched non-BS patients were enrolled. Metabolic profiling was performed using UPLC-MS. The ratio of subjects with a rough pulse and purple coloration of the tongue was higher in patients presenting with BS pattern. Through metabolomics analysis, 82 metabolites that differed significantly between the BS and non-BS pattern were identified, and the two groups were significantly separated using an orthogonal partial least square-discriminant analysis model (P < 0.001). Of these 82 metabolites, acetyl carnitine, leucine, kynurenine, phosphocholine, hexanoyl carnitine, and decanoyl carnitine were present in significantly higher levels in patients with a BS pattern than those with a non-BS pattern. Our results also demonstrated that seven plasma metabolites, including acyl-carnitines and kynurenine, were associated with a BS pattern, suggesting that variant plasma metabolic profiles may serve as a biomarker for diagnosis of BS in patients with cerebral infarction. PMID: 25834622 [PubMed - as supplied by publisher]

Nutrition and Metabolic Correlates of Obesity and Inflammation: Clinical Considerations. J Nutr. 2015 Apr 1; Authors: Johnson AR, Makowski L Abstract Since 1980, the global prevalence of obesity has doubled; in the United States, it has almost tripled. Billions of people are overweight and obese; the WHO reports that >65% of the world's population die of diseases related to overweight rather than underweight. Obesity is a complex disease that can be studied from "metropolis to metabolite"-that is, beginning at the policy and the population level through epidemiology and intervention studies; to bench work including preclinical models, tissue, and cell culture studies; to biochemical assays; and to metabolomics. Metabolomics is the next research frontier because it provides a real-time snapshot of biochemical building blocks and products of cellular processes. This report comments on practical considerations when conducting metabolomics research. The pros and cons and important study design concerns are addressed to aid in increasing metabolomics research in the United States. The link between metabolism and inflammation is an understudied phenomenon that has great potential to transform our understanding of immunometabolism in obesity, diabetes, cancer, and other diseases; metabolomics promises to be an important tool in understanding the complex relations between factors contributing to such diseases. PMID: 25833891 [PubMed - as supplied by publisher]

Whey Protein Supplementation Does Not Alter Plasma Branched-Chained Amino Acid Profiles but Results in Unique Metabolomics Patterns in Obese Women Enrolled in an 8-Week Weight Loss Trial. J Nutr. 2015 Apr;145(4):691-700 Authors: Piccolo BD, Comerford KB, Karakas SE, Knotts TA, Fiehn O, Adams SH Abstract BACKGROUND: It has been suggested that perturbations in branched-chain amino acid (BCAA) catabolism are associated with insulin resistance and contribute to elevated systemic BCAAs. Evidence in rodents suggests dietary protein rich in BCAAs can increase BCAA catabolism, but there is limited evidence in humans. OBJECTIVE: We hypothesize that a diet rich in BCAAs will increase BCAA catabolism, which will manifest in a reduction of fasting plasma BCAA concentrations. METHODS: The metabolome of 27 obese women with metabolic syndrome before and after weight loss was investigated to identify changes in BCAA metabolism using GC-time-of-flight mass spectrometry. Subjects were enrolled in an 8-wk weight-loss study including either a 20-g/d whey (whey group, n = 16) or gelatin (gelatin group, n = 11) protein supplement. When matched for total protein by weight, whey protein has 3 times the amount of BCAAs compared with gelatin protein. RESULTS: Postintervention plasma abundances of Ile (gelatin group: 637 ± 18, quantifier ion peak height ÷ 100; whey group: 744 ± 65), Leu (gelatin group: 1210 ± 33; whey group: 1380 ± 79), and Val (gelatin group: 2080 ± 59; whey group: 2510 ± 230) did not differ between treatment groups. BCAAs were significantly correlated with homeostasis model assessment of insulin resistance at baseline (r = 0.52, 0.43, and 0.49 for Leu, Ile, and Val, respectively; all, P < 0.05), but correlations were no longer significant at postintervention. Pro- and Cys-related pathways were found discriminant of whey protein vs. gelatin protein supplementation in multivariate statistical analyses. CONCLUSIONS: These findings suggest that BCAA metabolism is, at best, only modestly affected at a whey protein supplementation dose of 20 g/d. Furthermore, the loss of an association between postintervention BCAA and homeostasis model assessment suggests that factors associated with calorie restriction or protein intake affect how plasma BCAAs relate to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00739479. PMID: 25833773 [PubMed - as supplied by publisher]

Habitual Physical Activity and Plasma Metabolomic Patterns Distinguish Individuals with Low vs. High Weight Loss during Controlled Energy Restriction. J Nutr. 2015 Apr;145(4):681-690 Authors: Piccolo BD, Keim NL, Fiehn O, Adams SH, Van Loan MD, Newman JW Abstract BACKGROUND: Total weight loss induced by energy restriction is highly variable even under tightly controlled conditions. Identifying weight-loss discriminants would provide a valuable weight management tool and insights into body weight regulation. OBJECTIVE: This study characterized responsiveness to energy restriction in adults from variables including the plasma metabolome, endocrine and inflammatory markers, clinical indices, body composition, diet, and physical activity. METHODS: Data were derived from a controlled feeding trial investigating the effect of 3-4 dairy product servings in an energy-restricted diet (2092 kJ/d reduction) over 12 wk. Partial least squares regression was used to identify weight-loss discriminants in 67 overweight and obese adults. Linear mixed models were developed to identify discriminant variable differences in high- vs. low-weight-loss responders. RESULTS: Both pre- and postintervention variables (n = 127) were identified as weight-loss discriminants (root mean squared error of prediction = 1.85 kg; Q(2) = 0.43). Compared with low-responders (LR), high-responders (HR) had greater decreases in body weight (LR: 2.7 ± 1.6 kg; HR: 9.4 ± 1.8 kg, P < 0.01), BMI (in kg/m(2); LR: 1.0 ± 0.6; HR: 3.3 ± 0.5, P < 0.01), and total fat (LR: 2.2 ± 1.1 kg; HR: 8.0 ± 2.1 kg, P < 0.01). Significant group effects unaffected by the intervention were determined for the respiratory exchange ratio (LR: 0.86 ± 0.05; HR: 0.82 ± 0.03, P < 0.01), moderate physical activity (LR: 127 ± 52 min; HR: 167 ± 68 min, P = 0.02), sedentary activity (LR: 1090 ± 99 min; HR: 1017 ± 110 min, P = 0.02), and plasma stearate [LR: 102,000 ± 21,000 quantifier ion peak height (QIPH); HR: 116,000 ± 24,000 QIPH, P = 0.01]. CONCLUSIONS: Overweight and obese individuals highly responsive to energy restriction had accelerated reductions in adiposity, likely supported in part by higher lipid mobilization and combustion. A novel observation was that person-to-person differences in habitual physical activity and magnitude of weight loss were accompanied by unique blood metabolite signatures. This trial was registered at clinicaltrials.gov as NCT00858312. PMID: 25833772 [PubMed - as supplied by publisher]

Application of high-resolution mass spectrometry to measure low abundance isotope enrichment in individual muscle proteins. Anal Bioanal Chem. 2015 Apr 2; Authors: Hines KM, Ford GC, Klaus KA, Irving BA, Ford BL, Johnson KL, Lanza IR, Nair KS Abstract Stable isotope-labeled amino acids have long been used to measure the fractional synthesis rate of proteins, although the mass spectrometry platforms used for such analyses have changed throughout the years. More recently, tandem mass spectrometers such as triple quadrupoles have been accepted as the standard platform for enrichment measurement due to their sensitivity and the enhanced specificity offered by multiple reaction monitoring (MRM) experiments. The limit in the utility of such platforms for enrichment analysis occurs when measuring very low levels of enrichment from small amounts of sample, particularly proteins isolated from two-dimensional gel electrophoresis (2D-GE), where interference from contaminant ions impacts the sensitivity of the measurement. We therefore applied a high-resolution orbitrap mass spectrometer to the analysis of [ring-(13)C6]-phenylalanine enrichment in individual muscle proteins isolated with 2D-GE. Comparison of samples analyzed on both platforms revealed that the high-resolution MS has significantly improved sensitivity relative to the triple quadrupole MS at very low-level enrichments due to its ability to resolve interferences in the m/z dimension. At higher enrichment levels, enrichment measurements from the orbitrap platform showed significant correlation (R (2) > 0.5) with those of the triple quadrupole platform. Together, these results indicate that high-resolution MS platforms such as the orbitrap are not only as capable of performing isotope enrichment measurements as the more commonly preferred triple quadrupole instruments, but offer unparalleled advantages in terms of mass accuracy and sensitivity in the presence of similar-mass contaminants. PMID: 25832482 [PubMed - as supplied by publisher]

Related Articles Analyses of the Transcriptome and Metabolome Demonstrate That HIF1α Mediates Altered Tumor Metabolism in Clear Cell Renal Cell Carcinoma. PLoS One. 2015;10(4):e0120649 Authors: Minton DR, Fu L, Chen Q, Robinson BD, Gross SS, Nanus DM, Gudas LJ Abstract Hypoxia inducible factor 1 alpha (HIF1α) is a transcription factor that is frequently stabilized and active in human clear cell renal cell carcinoma (ccRCC). We have found that constitutively active HIF1α is sufficient to cause neoplastic transformation in a murine model of ccRCC termed the TRACK model. RNA sequencing (RNAseq) and untargeted metabolomics analyses of samples from TRACK kidneys demonstrate that HIF1α activates the transcription of genes that cause increased glucose uptake, glycolysis, and lactate production, as well as a decrease in the flux of pyruvate entering the tricarboxylic acid (TCA) cycle and a decrease in oxidative phosphorylation; these changes are identical to those observed in human ccRCC samples. These studies show that a constitutively active HIF1α promotes tumorigenesis in TRACK mice by mediating a metabolic switch to aerobic glycolysis, i.e., the Warburg effect, and suggest that TRACK mice are a valid model to test novel therapies targeting metabolic changes to inhibit human ccRCC. PMID: 25830305 [PubMed - as supplied by publisher]

Related Articles Evidence for a link between Gut Microbiota and Hypertension in the Dahl rat model. Physiol Genomics. 2015 Mar 31;:physiolgenomics.00136.2014 Authors: Mell B, Jala VR, Mathew AV, Byun J, Waghulde H, Zhang Y, Haribabu B, Vijay-Kumar M, Pennathur S, Joe B Abstract Gut microbiota play a critical role in maintaining physiological homeostasis. This study was designed to evaluate whether gut microbial composition impacts hypertension. 16S rRNA genes obtained from cecal samples of Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats, were sequenced. Bacteria of the phylum Bacteriodetes were higher in the S rats compared with the R rats. Further, the family S24-7 of the phylum Bacteriodetes and the family Veillonellaceae of the phylum Firmicutes were higher in the S rats compared to the R rats. Analyses of the various phylogenetic groups of cecal microbiota revealed significant differences between S and R rats. Both strains were maintained on a high-salt diet, administered antibiotics for ablation of microbiota, transplanted with S or R rat cecal contents and monitored for blood pressure (BP). Systolic BP of the R rats remained unaltered irrespective of S or R rat cecal transplantation. Surprisingly, compared to the S rats given S rat cecal content, systolic BP of the S rats given a single bolus of cecal content from R rats was consistently and significantly elevated during the rest of their life and had a shorter lifespan. Lower level of fecal bacteria of the family Veillonellaceae and increased plasma acetate and heptanoate were features associated with the increased BP observed in the S rats given R rat microbiota compared with the S rats given S rat microbiota. These data demonstrate a link between microbial content and BP regulation and because the S and R rats differ in their genomic composition, provide the necessary basis to further examine the relationship between the host genome and microbiome in the context of BP regulation in the Dahl rats. PMID: 25829393 [PubMed - as supplied by publisher]

Related Articles Women with preterm birth have a distinct cervico-vaginal metabolome. Am J Obstet Gynecol. 2015 Mar 28; Authors: Ghartey J, Bastek JA, Brown A, Anglim L, Elovitz MA Abstract OBJECTIVE: Metabolomics has the potential to reveal novel pathways involved in the pathogenesis of preterm birth (PTB). The objective of this study was to investigate if the cervico-vaginal (CV) metabolome was different in asymptomatic women destined to have a PTB compared to term birth. STUDY DESIGN: A nested case-control study was performed using CV fluid collected from a larger prospective cohort. CV fluid was collected between 20-24 weeks (V1) and 24-28 weeks (V2). The metabolome was compared between women with a spontaneous PTB (n=10) to women who delivered at term (n=10). Samples were extracted and prepared for analysis using a standard extraction solvent method (Metabolon®, Durham, NC). Global biochemical profiles were determined using GC/MS and UPLC MS/MS. ANOVA was used to detect differences in biochemical compounds between the groups. A false discovery rate was estimated to account for multiple comparisons. RESULT: A total of 313 biochemicals were identified in CV fluid. 82 biochemicals were different in the CV fluid at V1 in those destined to have a PTB compared to term birth while 48 were different at V2 (Table 1). Amino acid, carbohydrate, and peptide metabolites were distinct between women with and without PTB. CONCLUSION: These data suggest that the CV space is metabolically active during pregnancy. Changes in the CV metabolome may be observed weeks, if not months, prior to any clinical symptoms. Understanding the CV metabolome may hold promise for unraveling the pathogenesis of PTB and may provide novel biomarkers to identify women most at risk. PMID: 25827503 [PubMed - as supplied by publisher]

Related Articles Omics for aquatic ecotoxicology; Control of extraneous variability to enhance the analysis of environmental effects. Environ Toxicol Chem. 2015 Apr 1; Authors: Simmons DB, Benskin JP, Cosgrove JR, Duncker BP, Ekman DR, Martyniuk CJ, Sherry JP Abstract There are multiple sources of biological and technical variation in a typical ecotoxicology study that may not be revealed by traditional endpoints but that become apparent in an omics dataset. As researchers increasingly apply omics technologies to environmental studies, it will be necessary to challenge ourselves to understand and control the main source(s) of variability to facilitate meaningful interpretation of such data. For instance, can variability in omics studies be addressed by changing our approach to study design and data analysis? Are there statistical methods that we can employ to correctly interpret omics data and make use of unattributed, inherent variability? In the present article, we review experimental design and statistical considerations applicable to using omics methods in systems toxicology studies. In addition to highlighting potential sources that contribute to experimental variability, this review suggests strategies with which to reduce and/or control such variability so as to improve reliability, reproducibility, and ultimately the application of omics data for systems toxicology. This article is protected by copyright. All rights reserved. PMID: 25827364 [PubMed - as supplied by publisher]

Related Articles Resource recovery from wastewater: application of meta-omics to phosphorus and carbon management. Curr Opin Biotechnol. 2015 Mar 26;33:260-267 Authors: Sales CM, Lee PK Abstract A growing trend at wastewater treatment plants is the recovery of resources and energy from wastewater. Enhanced biological phosphorus removal and anaerobic digestion are two established biotechnology approaches for the recovery of phosphorus and carbon, respectively. Meta-omics approaches (meta-genomics, transcriptomics, proteomics, and metabolomics) are providing novel biological insights into these complex biological systems. In particular, genome-centric metagenomics analyses are revealing the function and physiology of individual community members. Querying transcripts, proteins and metabolites are emerging techniques that can inform the cellular responses under different conditions. Overall, meta-omics approaches are shedding light into complex microbial communities once regarded as 'blackboxes', but challenges remain to integrate information from meta-omics into engineering design and operation guidelines. PMID: 25827118 [PubMed - as supplied by publisher]