Consensus Clustering of temporal profiles for the identification of metabolic markers of pre-diabetes in childhood (EarlyBird 73)

In longitudinal clinical studies, methodologies available for the analysis of multivariate data with multivariate methods are relatively limited. Here, we present Consensus Clustering (CClust) a new computational method based on clustering of time pro les and posterior identi cation of correlation between clusters and predictors. Subjects are rst clustered in groups according to a response variable temporal pro le, using a robust consensus-based strategy. To discover which of the remaining variables are associated with the resulting groups, a non-parametric hypothesis test is performed between groups at every time point, and then the results are aggregated according to the Fisher method. Our approach is tested through its application to the EarlyBird cohort database, which contains temporal variations of clinical, metabolic, and anthropometric pro les in a population of 150 children followed-up annually from age 5 to age 16. Our results show that our consensus-based method is able to overcome the problem of the approach-dependent results produced by current clustering algorithms, producing groups de ned according to Insulin Resistance (IR) and biological age (Tanner Score). Moreover, it provides meaningful biological results con rmed by hypothesis testing with most of the main clinical variables. These results position CClust as a valid alternative for the analysis of multivariate longitudinal data

Metabonomics in neonatal nutrition research

Maternal obesity and early post-natal nutrition might associate with increased obesity risk in later life. We have investigated the effect of breastfeeding and infant formulas differing in protein content on the urinary and fecal metabolism of term infants born from overweight and obese mothers using a metabonomic approach. Metabolic differences were observed between breast and formula fed infants both in urine and stool samples. Metabolic profiles of formula fed infants exhibited a distinct metabolic pattern that was associated with the processing of dietary proteins from the host and the gut microbiota. Metabonomics appears as a powerful tool to measure the physiological response to infant formula versus the gold standard breastfeeding. In future, nutritional phenotyping will combine metabonomics and nutritional profiling to study specific nutritional requirements and measure the efficacy of tailored nutritional interventions on growth and development endpoints. It will then open novel opportunities to develop targeted nutritional solutions for health maintenance and disease prevention.   Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy) · October 26th-31st, 2015 · From the womb to the adult Guest Editors: Vassilios Fanos (Cagliari, Italy), Michele Mussap (Genoa, Italy), Antonio Del Vecchio (Bari, Italy), Bo Sun (Shanghai, China), Dorret I. Boomsma (Amsterdam, the Netherlands), Gavino Faa (Cagliari, Italy), Antonio Giordano (Philadelphia, USA

Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains

Calorie restriction (CR) has long been used to study lifespan effects and oppose the development of a broad array of age-related biological and pathological changes (increase healthspan). Yet, a comprehensive comparison of the metabolic phenotype across different genetic backgrounds to identify common metabolic markers affected by CR is still lacking. Using a system biology approach comprising metabonomics and liver transcriptomics we revealed the effect of CR across multiple mouse strains (129S1/SvlmJ, C57BL6/J, C3H/HeJ, CBA/J, DBA/2J, JC3F1/J). Oligonucleotide microarrays identified 76 genes as differentially expressed in all six strains confirmed. These genes were subjected to quantitative RT-PCR analysis in the C57BL/6J mouse strain, and a CR-induced change expression was confirmed for 14 genes. To fully depict the metabolic pathways affected by CR and complement the changes observed through differential gene expression, the metabolome of C57BL6/J was further characterized in liver tissues, urine and plasma levels using a combination or targeted mass spectrometry and proton nuclear magnetic resonance spectroscopy. Overall, our integrated approach commonly confirms that energy metabolism, stress response, lipids regulators and the insulin/IGF-1 are key determinants factors involved in CR regulation

Balgacyclamides, Antiplasmodial Heterocyclic Peptides fromMicrocystis aeruguinosaEAWAG 251

The isolation and structural characterization of three new heterocyclic and macrocyclic peptides, balgacyclamides A-C, from Microcystis aeruginosa EAWAG 251 are reported. The constitutions were determined by 2D-NMR methods and mass spectrometry, and the configurations were assigned after ozonolysis and hydrolysis by HPLC-MS methods using Marfey's method as well as GC-MS using authentic standards. Balgacyclamides A and B were active against Plasmodium falciparum K1 in the low micromolar range, while displaying low toxicity to rat myoblasts

Transcriptomics and Metabonomics Identify Essential Metabolic Signatures in Calorie Restriction (CR) Regulation across Multiple Mouse Strains

Calorie restriction (CR) has long been used to study lifespan effects and oppose the development of a broad array of age-related biological and pathological changes (increase healthspan). Yet, a comprehensive comparison of the metabolic phenotype across different genetic backgrounds to identify common metabolic markers affected by CR is still lacking. Using a system biology approach comprising metabonomics and liver transcriptomics we revealed the effect of CR across multiple mouse strains (129S1/SvlmJ, C57BL6/J, C3H/HeJ, CBA/J, DBA/2J, JC3F1/J). Oligonucleotide microarrays identified 76 genes as differentially expressed in all six strains confirmed. These genes were subjected to quantitative RT-PCR analysis in the C57BL/6J mouse strain, and a CR-induced change expression was confirmed for 14 genes. To fully depict the metabolic pathways affected by CR and complement the changes observed through differential gene expression, the metabolome of C57BL6/J was further characterized in liver tissues, urine and plasma levels using a combination or targeted mass spectrometry and proton nuclear magnetic resonance spectroscopy. Overall, our integrated approach commonly confirms that energy metabolism, stress response, lipids regulators and the insulin/IGF-1 are key determinants factors involved in CR regulation

Urinary metabolomics in term newborns delivered spontaneously or with cesarean section: preliminary data

Introduction: In the last years the uncritical attitude towards cesarean section (CS) has been associated with the fast emergence of ‘modern’ diseases such as early pediatric obesity, asthma, type 2 diabetes mellitus and dermatitis. Increasing evidence shows that babies born at term by vaginal delivery (VD) have a different physiology at birth, with subsequent influence on adult health. In relation to these short-term physiological changes, in the present study we aimed at assessing the influence of the mode of delivery in term newborns on the first 24 hours metabolism of neonates. Material and methods: This study was carried out on urine samples from 42 patients admitted to the Neonatal Intensive Unit and Neonatal Pathology of “S. Giovanni Calibita” Hospital Fatebenefratelli (Rome, Italy). According to the type of delivery, term neonates with similar gestational age and birthweight were divided in two groups: (1) born by spontaneous VD, (2) born by elective CS. Urine samples, collected at birth by a non-invasive method, were subjected to proton Nuclear Magnetic Resonance spectroscopy. Results: CS newborns showed lower fatty acid omega oxidation, as evidenced by lower urinary excretion of dicarboxylic acids. This metabolic signature supports current evidence that babies delivered by CS have lower body temperature and perturbed thermogenesis. CS associates also with hypoglycaemia and altered endocrine profile, which linked to changes in central energy metabolic pathways (Krebs and Cori Cycles). Lung function may be reduced in infants born by CS, primarily due to delayed clearance of lung liquid, and surfactant insufficiency, which might be reflected in different urinary excretion of myo-inositol and choline – two intermediates in lung surfactant metabolism. Conclusion: Non-invasive urine metabolic phenotyping of children born by different mode of delivery provides relevant readouts to assess metabolic requirements associated with major physiological functions during this critical period of metabolic adaptation

High-resolution quantitative metabolome analysis of urine by automated flow injection NMR

[Image: see text] Metabolism is essential to understand human health. To characterize human metabolism, a high-resolution read-out of the metabolic status under various physiological conditions, either in health or disease, is needed. Metabolomics offers an unprecedented approach for generating system-specific biochemical definitions of a human phenotype through the capture of a variety of metabolites in a single measurement. The emergence of large cohorts in clinical studies increases the demand of technologies able to analyze a large number of measurements, in an automated fashion, in the most robust way. NMR is an established metabolomics tool for obtaining metabolic phenotypes. Here, we describe the analysis of NMR-based urinary profiles for metabolic studies, challenged to a large human study (3007 samples). This method includes the acquisition of nuclear Overhauser effect spectroscopy one-dimensional and J-resolved two-dimensional (J-Res-2D) (1)H NMR spectra obtained on a 600 MHz spectrometer, equipped with a 120 μL flow probe, coupled to a flow-injection analysis system, in full automation under the control of a sampler manager. Samples were acquired at a throughput of ∼20 (or 40 when J-Res-2D is included) min/sample. The associated technical analysis error over the full series of analysis is 12%, which demonstrates the robustness of the method. With the aim to describe an overall metabolomics workflow, the quantification of 36 metabolites, mainly related to central carbon metabolism and gut microbial host cometabolism, was obtained, as well as multivariate data analysis of the full spectral profiles. The metabolic read-outs generated using our analytical workflow can therefore be considered for further pathway modeling and/or biological interpretation