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      Probiotic modulation of symbiotic gut microbial–host metabolic interactions in a humanized microbiome mouse model

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          The transgenomic metabolic effects of exposure to either Lactobacillus paracasei or Lactobacillus rhamnosus probiotics have been measured and mapped in humanized extended genome mice (germ-free mice colonized with human baby flora). Statistical analysis of the compartmental fluctuations in diverse metabolic compartments, including biofluids, tissue and cecal short-chain fatty acids (SCFAs) in relation to microbial population modulation generated a novel top-down systems biology view of the host response to probiotic intervention. Probiotic exposure exerted microbiome modification and resulted in altered hepatic lipid metabolism coupled with lowered plasma lipoprotein levels and apparent stimulated glycolysis. Probiotic treatments also altered a diverse range of pathways outcomes, including amino-acid metabolism, methylamines and SCFAs. The novel application of hierarchical-principal component analysis allowed visualization of multicompartmental transgenomic metabolic interactions that could also be resolved at the compartment and pathway level. These integrated system investigations demonstrate the potential of metabolic profiling as a top-down systems biology driver for investigating the mechanistic basis of probiotic action and the therapeutic surveillance of the gut microbial activity related to dietary supplementation of probiotics.

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          Most cited references 77

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          Modified Spin-Echo Method for Measuring Nuclear Relaxation Times

           S. Meiboom,  D. Gill (1958)
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            750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma.

            High-resolution 750 MHz 1H NMR spectra of control human blood plasma have been measured and assigned by the concerted use of a range of spin-echo, two-dimensional J-resolved, and homonuclear and heteronuclear (1H-13C) correlation methods. The increased spectral dispersion and sensitivity at 750 MHz enable the assignment of numerous 1H and 13C resonances from many molecular species that cannot be detected at lower frequencies. This work presents the most comprehensive assignment of the 1H NMR spectra of blood plasma yet achieved and includes the assignment of signals from 43 low M(r) metabolites, including many with complex or strongly coupled spin systems. New assignments are also provided from the 1H and 13C NMR signals from several important macromolecular species in whole blood plasma, i.e., very-low-density, low-density, and high-density lipoproteins, albumin, and alpha 1-acid glycoprotein. The temperature dependence of the one-dimensional and spin-echo 750 MHz 1H NMR spectra of plasma was investigated over the range 292-310 K. The 1H NMR signals from the fatty acyl side chains of the lipoproteins increased substantially with temperature (hence also molecular mobility), with a disproportionate increase from lipids in low-density lipoprotein. Two-dimensional 1H-13C heteronuclear multiple quantum coherence spectroscopy at 292 and 310 K allowed both the direct detection of cholesterol and choline species bound in high-density lipoprotein and the assignment of their signals and confirmed the assignment of most of the lipoprotein resonances.
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              Opinion: understanding 'global' systems biology: metabonomics and the continuum of metabolism.


                Author and article information

                Mol Syst Biol
                Molecular Systems Biology
                Nature Publishing Group
                15 January 2008
                : 4
                : 157
                [1 ]Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, London, UK
                [2 ]Nestlé Research Center, Lausanne, Switzerland
                [3 ]AcurePharmaAB, Uppsala, Sweden
                [4 ]Department of Medicinal Chemistry, BMC, Uppsala University, Uppsala, Sweden
                Author notes
                [a ]Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK. Tel.: +44 20 7594 3195; Fax: +44 20 7594 3226; j.nicholson@ 123456imperial.ac.uk
                Copyright © 2007, EMBO and Nature Publishing Group

                This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution and reproduction in any medium, provided the original author and source are credited. Creation of derivative works is permitted but the resulting work may be distributed only under the same or similar licence to this one. This licence does not permit commercial exploitation without specific permission.

                Page count
                Pages: 1

                Quantitative & Systems biology

                probiotics, metabonomics, uplc-ms, nmr spectroscopy, microbiome


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