Imperial College London

ProfessorElaineHolmes

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3220elaine.holmes

 
 
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Location

 

661Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

747 results found

Rezzonico E, Mestdagh R, Delley M, Combremont S, Dumas M-E, Holmes E, Nicholson J, Bibiloni Ret al., 2011, Bacterial adaptation to the gut environment favors successful colonization Microbial and metabonomic characterization of a simplified microbiota mouse model, GUT MICROBES, Vol: 2, Pages: 307-318, ISSN: 1949-0976

Journal article

Claus SP, Ellero SL, Berger B, Krause L, Bruttin A, Molina J, Paris A, Want EJ, de Waziers I, Cloarec O, Richards SE, Wang Y, Dumas M-E, Ross A, Rezzi S, Kochhar S, Van Bladeren P, Lindon JC, Holmes E, Nicholson JKet al., 2011, Colonization-induced host-gut microbial metabolic interaction., mBio, Vol: 2, Pages: e00271-e00210

UNLABELLED: The gut microbiota enhances the host's metabolic capacity for processing nutrients and drugs and modulate the activities of multiple pathways in a variety of organ systems. We have probed the systemic metabolic adaptation to gut colonization for 20 days following exposure of axenic mice (n = 35) to a typical environmental microbial background using high-resolution (1)H nuclear magnetic resonance (NMR) spectroscopy to analyze urine, plasma, liver, kidney, and colon (5 time points) metabolic profiles. Acquisition of the gut microbiota was associated with rapid increase in body weight (4%) over the first 5 days of colonization with parallel changes in multiple pathways in all compartments analyzed. The colonization process stimulated glycogenesis in the liver prior to triggering increases in hepatic triglyceride synthesis. These changes were associated with modifications of hepatic Cyp8b1 expression and the subsequent alteration of bile acid metabolites, including taurocholate and tauromuricholate, which are essential regulators of lipid absorption. Expression and activity of major drug-metabolizing enzymes (Cyp3a11 and Cyp2c29) were also significantly stimulated. Remarkably, statistical modeling of the interactions between hepatic metabolic profiles and microbial composition analyzed by 16S rRNA gene pyrosequencing revealed strong associations of the Coriobacteriaceae family with both the hepatic triglyceride, glucose, and glycogen levels and the metabolism of xenobiotics. These data demonstrate the importance of microbial activity in metabolic phenotype development, indicating that microbiota manipulation is a useful tool for beneficially modulating xenobiotic metabolism and pharmacokinetics in personalized health care. IMPORTANCE: Gut bacteria have been associated with various essential biological functions in humans such as energy harvest and regulation of blood pressure. Furthermore, gut microbial colonization occurs after birth in parallel with other

Journal article

Merrifield CA, Lewis M, Claus SP, Beckonert OP, Dumas M, Duncker S, Kochhar S, Rezzi S, Lindon JC, Bailey M, Holmes E, Nicholson JKet al., 2011, A metabolic system-wide characterisation of the pig: a model for human physiology, Molecular BioSystems, Vol: 7, Pages: 2577-2588, ISSN: 1742-206X

The pig is a single-stomached omnivorous mammal and is an important model of human disease and nutrition. As such, it is necessary to establish a metabolic framework from which pathology-based variation can be compared. Here, a combination of one and two-dimensional 1H and 13C nuclear magnetic resonance spectroscopy (NMR) and high-resolution magic angle spinning (HR-MAS) NMR was used to provide a systems overview of porcine metabolism via characterisation of the urine, serum, liver and kidney metabolomes. The metabolites observed in each of these biological compartments were found to be qualitatively comparable to the metabolic signature of the same biological matrices in humans and rodents. The data were modelled using a combination of principal components analysis and Venn diagram mapping. Urine represented the most metabolically distinct biological compartment studied, with a relatively greater number of NMR detectable metabolites present, many of which are implicated in gut-microbial co-metabolic processes. The major inter-species differences observed were in the phase II conjugation of extra-genomic metabolites; the pig was observed to conjugate p-cresol, a gut microbial metabolite of tyrosine, with glucuronide rather than sulfate as seen in man. These observations are important to note when considering the translatability of experimental data derived from porcine models.

Journal article

Gavaghan CL, Li JV, Hadfield ST, Hole S, Nicholson JK, Wilson ID, Howe PWA, Stanley PD, Holmes Eet al., 2010, Application of NMR-based Metabolomics to the Investigation of Salt Stress in Maize (Zea mays), PHYTOCHEMICAL ANALYSIS, Vol: 22, Pages: 214-224, ISSN: 0958-0344

Journal article

Fonville JM, Richards SE, Barton RH, Boulange CL, Ebbels TMD, Nicholson JK, Holmes EC, Dumas MEet al., 2010, The Evolution of Partial Least Squares Models and Related Chemometric Approaches in Metabonomics and Metabolic Phenotyping, J. Chemometrics, Vol: 24, Pages: 636-649

Metabonomics is a key element in systems biology, and with current analytical methods, generates vast amounts ofquantitative or qualitative metabolic data. Understanding of the global function of the living organism can beachieved by integration of ‘omics’ approaches including metabonomics, genomics, transcriptomics and proteomics,increasing the complexity of the full data sets. Multivariate statistical approaches are well suited to extract thecharacterizing metabolic information associated with each level of dynamic process. In this review, we discusstechniques that have evolved from principal component analysis and partial least squares (PLS) methods with a focuson improved interpretation and modeling with respect to biomarker recovery and data visualization in the context ofmetabonomic applications. Visualization is of paramount importance to investigate complex metabolic signatures,the power and potential of which is illustrated with key papers. Recent improvements based on the removal oforthogonal variation are discussed in terms of interpretation enhancement, and are supported by relevantapplications. Flexibility of PLS methods in general and of O-PLS in particular allows implementation of derivativemethods such as O2-PLS, O-PLS-variance components, nonlinear methods, and batch modeling to improve analysis ofcomplex data sets, which facilitates extraction of information related to subtle biological processes. These approachescan be used to address issues present in complex multi-factorial data sets. Thus, we highlight the key advantages andlimitations of the different latent variable applications for top-down systems biology and assess the differencesbetween the methods available.

Journal article

Yap IKS, Brown IJ, Chan Q, Wijeyesekera A, Garcia-Perez I, Bictash M, Loo RL, Chadeau-Hyam M, Ebbeis T, De Iorio M, Maibaum E, Zhao L, Kesteloot H, Daviglus ML, Stamler J, Nicholson JK, Elliott P, Holmes Eet al., 2010, Metabolome-Wide Association Study Identifies Multiple Biomarkers that Discriminate North and South Chinese Populations at Differing Risks of Cardiovascular Disease INTERMAP Study, JOURNAL OF PROTEOME RESEARCH, Vol: 9, Pages: 6647-6654, ISSN: 1535-3893

Journal article

Richards SE, Dumas M-E, Fonville JM, Ebbels TMD, Holmes E, Nicholson JKet al., 2010, Intra- and inter-omic fusion of metabolic profiling data in a systems biology framework, CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS, Vol: 104, Pages: 121-131, ISSN: 0169-7439

Journal article

Vecht JA, Saso S, Rao C, Dimopoulos K, Grapsa J, Terracciano CM, Peters NS, Nihoyannopoulos P, Holmes E, Gatzoulis MA, Athanasiou Tet al., 2010, Atrial septal defect closure is associated with a reduced prevalence of atrial tachyarrhythmia in the short to medium term: a systematic review and meta-analysis, HEART, Vol: 96, Pages: 1789-1797, ISSN: 1355-6037

Journal article

Ashrafian H, Athanasiou T, JV L, Bueter M, Ahmed K, Nagpal K, Holmes E, Darzi A, Bloom SRet al., 2010, Diabetes resolution and hyperinsulinaemia after metabolic Roux-en-Y gastric bypass, Obes Rev

Journal article

Bictash M, Ebbels TM, Chan Q, Loo RL, Yap IKS, Brown IJ, de Iorio M, Daviglus ML, Holmes E, Stamler J, Nicholson JK, Elliott Pet al., 2010, Opening up the "Black Box": Metabolic phenotyping and metabolome-wide association studies in epidemiology, JOURNAL OF CLINICAL EPIDEMIOLOGY, Vol: 63, Pages: 970-979, ISSN: 0895-4356

Journal article

Chadeau-Hyam M, Ebbels TMD, Brown IJ, Chan Q, Stemler J, Huang CC, Daviglus ML, Ueshima H, Zhao L, Holmes E, Nicholson JK, Elliott P, De Iorio Met al., 2010, Metabolic Profiling and the Metabolome-Wide Association Study: Significance Level For Biomarker Identification, JOURNAL OF PROTEOME RESEARCH, Vol: 9, Pages: 4620-4627, ISSN: 1535-3893

Journal article

Heinzmann SS, Brown IJ, Chan Q, Bictash M, Dumas M-E, Kochhar S, Stamler J, Holmes E, Elliott P, Nicholson JKet al., 2010, Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption, AMERICAN JOURNAL OF CLINICAL NUTRITION, Vol: 92, Pages: 436-443, ISSN: 0002-9165

Journal article

Holmes E, 2010, The evolution of metabolic profiling in parasitology, PARASITOLOGY, Vol: 137, Pages: 1437-1449, ISSN: 0031-1820

Journal article

Garcia-Perez I, Angulo S, Utzinger J, Holmes E, Legido-Quigley C, Barbas Cet al., 2010, Chemometric and biological validation of a capillary electrophoresis metabolomic experiment of <i>Schistosoma mansoni</i> infection in mice, ELECTROPHORESIS, Vol: 31, Pages: 2338-2348, ISSN: 0173-0835

Journal article

Legido-Quigley C, Stella C, Perez-Jimenez F, Lopez-Miranda J, Ordovas J, Powell J, van-der-Ouderaa F, Ware L, Lindon JC, Nicholson JK, Holmes Eet al., 2010, Liquid chromatography-mass spectrometry methods for urinary biomarker detection in metabonomic studies with application to nutritional studies, BIOMEDICAL CHROMATOGRAPHY, Vol: 24, Pages: 737-743, ISSN: 0269-3879

Journal article

Saric J, Li JV, Utzinger J, Wang Y, Keiser J, Dirnhofer S, Beckonert O, Sharabiani MT, Fonville JM, Nicholson JK, Holmes Eet al., 2010, Systems parasitology: effects of Fasciola hepatica on the neurochemical profile in the rat brain., Mol Syst Biol, Vol: 6

We characterize the integrated response of a rat host to the liver fluke Fasciola hepatica using a combination of (1)H nuclear magnetic resonance spectroscopic profiles (liver, kidney, intestine, brain, spleen, plasma, urine, feces) and multiplex cytokine markers of systemic inflammation. Multivariate mathematical models were built to describe the main features of the infection at the systems level. In addition to the expected modulation of hepatic choline and energy metabolism, we found significant perturbations of the nucleotide balance in the brain, together with increased plasma IL-13, suggesting a shift toward modulation of immune reactions to minimize inflammatory damage, which may favor the co-existence of the parasite in the host. Subsequent analysis of brain extracts from other trematode infection models (i.e. Schistosoma mansoni, and Echinostoma caproni) did not elicit a change in neural nucleotide levels, indicating that the neural effects of F. hepatica infection are specific. We propose that the topographically extended response to invasion of the host as characterized by the modulated global metabolic phenotype is stratified across several bio-organizational levels and reflects the direct manipulation of host-nucleotide balance.

Journal article

Veselkov KA, Pahomov VI, Lindon JC, Volynkin VS, Crockford D, Osipenko GS, Davies DB, Barton RH, Bang J-W, Holmes E, Nicholson JKet al., 2010, A Metabolic Entropy Approach for Measurements of Systemic Metabolic Disruptions in Patho-Physiological States, JOURNAL OF PROTEOME RESEARCH, Vol: 9, Pages: 3537-3544, ISSN: 1535-3893

Journal article

Want EJ, Coen M, Masson P, Keun HC, Pearce JTM, Reily MD, Robertson DG, Rohde CM, Holmes E, Lindon JC, Plumb RS, Nicholson JKet al., 2010, Ultra Performance Liquid Chromatography-Mass Spectrometry Profiling of Bile Acid Metabolites in Biofluids: Application to Experimental Toxicology Studies, ANALYTICAL CHEMISTRY, Vol: 82, Pages: 5282-5289, ISSN: 0003-2700

Journal article

Yap IKS, Angley M, Veselkov KA, Holmes E, Lindon JC, Nicholson JKet al., 2010, Urinary Metabolic Phenotyping Differentiates Children with Autism from Their Unaffected Siblings and Age-Matched Controls, JOURNAL OF PROTEOME RESEARCH, Vol: 9, Pages: 2996-3004, ISSN: 1535-3893

Journal article

Saric J, Li JV, Swann JR, Utzinger J, Calvert G, Nicholson JK, Dirnhofer S, Dallman MJ, Bictash M, Holmes Eet al., 2010, Integrated Cytokine and Metabolic Analysis of Pathological Responses to Parasite Exposure in Rodents, JOURNAL OF PROTEOME RESEARCH, Vol: 9, Pages: 2255-2264, ISSN: 1535-3893

Journal article

Wu J-F, Holmes E, Xue J, Xiao S-H, Singer BH, Tang H-R, Utzinger J, Wang Y-Let al., 2010, Metabolic alterations in the hamster co-infected with <i>Schistosoma japonicum</i> and <i>Necator americanus</i>, INTERNATIONAL JOURNAL FOR PARASITOLOGY, Vol: 40, Pages: 695-703, ISSN: 0020-7519

Journal article

Fonville JM, Maher AD, Coen M, Holmes E, Lindon JC, Nicholson JKet al., 2010, Evaluation of Full-Resolution <i>J</i>-Resolved <SUP>1</SUP>H NMR Projections of Biofluids for Metabonomics Information Retrieval and Biomarker Identification, ANALYTICAL CHEMISTRY, Vol: 82, Pages: 1811-1821, ISSN: 0003-2700

Journal article

Bollard ME, Contel NR, Ebbels TMD, Smith L, Beckonert O, Cantor GH, Lehman-McKeeman L, Holmes EC, Lindon JC, Nicholson JK, Keun HCet al., 2010, NMR-Based Metabolic Profiling Identifies Biomarkers of Liver Regeneration Following Partial Hepatectomy in the Rat, JOURNAL OF PROTEOME RESEARCH, Vol: 9, Pages: 59-69, ISSN: 1535-3893

Journal article

Wang Y, Li JV, Saric J, Keiser J, Wu J, Utzinger J, Holmes Eet al., 2010, Advances in metabolic profiling of experimental nematode and trematode infections., Advances in Parasitology, Vol: 73, Pages: 373-404

Journal article

Beckonert O, Coen M, Keun HC, Wang Y, Ebbels TMD, Holmes E, Lindon JC, Nicholson JKet al., 2010, High-resolution magic-angle-spinning NMR spectroscopy for metabolic profiling of intact tissues, NATURE PROTOCOLS, Vol: 5, Pages: 1019-1032, ISSN: 1754-2189

Journal article

Want EJ, Wilson ID, Gika H, Theodoridis G, Plumb RS, Shockcor J, Holmes E, Nicholson JKet al., 2010, Global metabolic profiling procedures for urine using UPLC-MS, NATURE PROTOCOLS, Vol: 5, Pages: 1005-1018, ISSN: 1754-2189

Journal article

Saidin NA, Holmes E, Randall T, Takayama T, Gooderham NJet al., 2010, Extract of Malaysian Kratom and its major alkaloid, mitragynine: Is their cytotoxicity mediated by opioid receptors?

Conference paper

Kinross J, Vernazza J, Holloway P, Holmes E, Darzi Aet al., 2010, Metabonomic profiling of plasma in secondary peritonitis: A novel diagnostic and prognostic strategy based on systems metabolism, Electronic Poster of Distinction in Association-of-Surgeons-of-Great-Britain-and-Ireland-International-Surgical-Congress, Publisher: WILEY-BLACKWELL, Pages: 80-80, ISSN: 0007-1323

Conference paper

Hong Y-S, Coen M, Rhode CM, Reily MD, Robertson DG, Holmes E, Lindon JC, Nicholson JKet al., 2009, Chemical shift calibration of <SUP>1</SUP>H MAS NMR liver tissue spectra exemplified using a study of glycine protection of galactosamine toxicity, MAGNETIC RESONANCE IN CHEMISTRY, Vol: 47, Pages: S47-S53, ISSN: 0749-1581

Journal article

Wang Y, Xiao S-H, Xue J, Singer BH, Utzinger J, Holmes Eet al., 2009, Systems Metabolic Effects of a <i>Necator americanus</i> Infection in Syrian Hamster, JOURNAL OF PROTEOME RESEARCH, Vol: 8, Pages: 5442-5450, ISSN: 1535-3893

Journal article

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