James M Kinross

Publications (7)92.68 Total impact

• Article: (1)H HR-MAS NMR Spectroscopy of Tumor Induced Local Metabolic "Field-Effects" enables Colorectal Cancer Staging and Prognostication.

  Beatriz Jimenez, Reza Mirnezami, James M Kinross, Olivier Cloarec, Hector Charles Keun, Elaine Holmes, Robert D Goldin, Paul Ziprin, Ara Darzi, Jeremy Kirk Nicholson
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  ABSTRACT: Colorectal Cancer (CRC) is a major cause of morbidity and mortality in developed countries. Despite operative advances and the widespread adoption of combined-modality treatment, 5-year survival rarely exceeds 60%. Improving our understanding of the biological processes involved in CRC development and progression will help generate new diagnostic and prognostic approaches. Previous studies have identified altered metabolism as a common feature in carcinogenesis, and quantitative measurement of this altered activity (metabonomics/metabolomics) has the potential to generate novel metabolite-based biomarkers for CRC diagnosis, staging and prognostication. In the present study we applied high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy to analyze metabolites in intact tumor samples (n=83) and samples of adjacent mucosa (n=87) obtained from 26 patients undergoing surgical resection for CRC. Orthogonal partial least squares discriminant analysis (OPLS-DA) of metabolic profiles identified marked biochemical differences between cancer tissue and adjacent mucosa (R(2)=0.72; Q(2)=0.45; AUC=0.91). Taurine, isoglutamine, choline, lactate, phenylalanine, tyrosine (increased concentrations in tumor tissue) together with lipids and triglycerides (decreased concentrations in tumor tissue) were the most discriminant metabolites between the two groups in the model. In addition tumor tissue metabolic profiles were able to distinguish between tumors of different T- and N-stage according to TNM classification. Moreover, we found that tumor-adjacent mucosa (10 cm from the tumor margin) harbors unique metabolic field changes that distinguish tumors according to T- and N- stage with higher predictive capability than tumor tissue itself, and are accurately predictive of 5-year survival (AUC=0.88), offering a highly novel means of tumor classification and prognostication in CRC.
  Journal of Proteome Research 12/2012; · 5.11 Impact Factor
• Article: Metabolic phenotyping in clinical and surgical environments.

  Jeremy K Nicholson, Elaine Holmes, James M Kinross, Ara W Darzi, Zoltan Takats, John C Lindon
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  ABSTRACT: Metabolic phenotyping involves the comprehensive analysis of biological fluids or tissue samples. This analysis allows biochemical classification of a person's physiological or pathological states that relate to disease diagnosis or prognosis at the individual level and to disease risk factors at the population level. These approaches are currently being implemented in hospital environments and in regional phenotyping centres worldwide. The ultimate aim of such work is to generate information on patient biology using techniques such as patient stratification to better inform clinicians on factors that will enhance diagnosis or the choice of therapy. There have been many reports of direct applications of metabolic phenotyping in a clinical setting.
  Nature 11/2012; 491(7424):384-392. · 36.28 Impact Factor
• Article: Implementation of molecular phenotyping approaches in the personalized surgical patient journey.

  Reza Mirnezami, James M Kinross, Panagiotis A Vorkas, Robert Goldin, Elaine Holmes, Jeremy Nicholson, Ara Darzi
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  ABSTRACT: The present review describes commonly employed metabolic profiling platforms and discusses the current and likely future application of these technologies in surgery. The metabolic adaptations that occur in response to surgical illness and trauma are incompletely understood. Evaluating these will be critical to the development of personalized surgical health solutions. Metabonomics is an advancing field in systems biology, which provides a means of interrogating these metabolic shifts. Recent literature regarding metabolic profiling technologies and their applications in surgical practice are discussed. Future strategies are proposed for the incorporation of these and next-generation technologies in the evaluation of all steps in the patient surgical pathway. Metabolite-based profiling has provided valuable insights into the metabolic irregularities that occur in cancer development and progression across a variety of cancer subclasses including colorectal, breast, prostate, and lung cancers. In addition, metabolic modeling has shown considerable promise in other surgical conditions including trauma and sepsis and in the assessment of pharmacotherapeutic efficacy. Metabonomics offers a posttranscriptional view of system activity providing functional information downstream of the genome and proteome. Information at this level will provide the surgeon with a novel means of evaluating major socioeconomic problems such as cancer and sepsis. In addition, the rapid nature of emerging next generation profiling platforms provides a viable means of "real-time" perioperative metabolic assessment and optimization.
  Annals of surgery 12/2011; 255(5):881-9. · 7.90 Impact Factor
• Article: Metabolic phenotyping for monitoring surgical patients.

  James M Kinross, Elaine Holmes, Ara W Darzi, Jeremy K Nicholson
  The Lancet 05/2011; 377(9780):1817-9. · 38.28 Impact Factor
• Source

  Available from: PubMed Central

  Article: Gut microbiome-host interactions in health and disease.

  James M Kinross, Ara W Darzi, Jeremy K Nicholson
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  ABSTRACT: The gut microbiome is the term given to describe the vast collection of symbiotic microorganisms in the human gastrointestinal system and their collective interacting genomes. Recent studies have suggested that the gut microbiome performs numerous important biochemical functions for the host, and disorders of the microbiome are associated with many and diverse human disease processes. Systems biology approaches based on next generation 'omics' technologies are now able to describe the gut microbiome at a detailed genetic and functional (transcriptomic, proteomic and metabolic) level, providing new insights into the importance of the gut microbiome in human health, and they are able to map microbiome variability between species, individuals and populations. This has established the importance of the gut microbiome in the disease pathogenesis for numerous systemic disease states, such as obesity and cardiovascular disease, and in intestinal conditions, such as inflammatory bowel disease. Thus, understanding microbiome activity is essential to the development of future personalized strategies of healthcare, as well as potentially providing new targets for drug development. Here, we review recent metagenomic and metabonomic approaches that have enabled advances in understanding gut microbiome activity in relation to human health, and gut microbial modulation for the treatment of disease. We also describe possible avenues of research in this rapidly growing field with respect to future personalized healthcare strategies.
  Genome Medicine 03/2011; 3(3):14.
• Article: Global metabolic phenotyping in an experimental laparotomy model of surgical trauma.

  James M Kinross, Nawar Alkhamesi, Richard H Barton, David B Silk, Ivan K S Yap, Ara W Darzi, Elaine Holmes, Jeremy K Nicholson
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  ABSTRACT: Surgical trauma initiates a complex series of metabolic host responses designed to maintain homeostasis and ensure survival. (1)H NMR spectroscopy was applied to intraoperative urine and plasma samples as part of a strategy to analyze the metabolic response of Wistar rats to a laparotomy model. Spectral data were analyzed by multivariate statistical analysis. Principal component analysis (PCA) confirmed that surgical injury is responsible for the majority of the metabolic variability demonstrated between animals (R² Urine = 81.2% R² plasma = 80%). Further statistical analysis by orthogonal projection to latent structure discriminant analysis (OPLS-DA) allowed the identification of novel urinary metabolic markers of surgical trauma. Urinary levels of taurine, glucose, urea, creatine, allantoin, and trimethylamine-N-oxide (TMAO) were significantly increased after surgery whereas citrate and 2-oxoglutarate (2-OG) negatively correlated with the intraoperative state as did plasma levels of betaine and tyrosine. Plasma levels of lipoproteins such as VLDL and LDL also rose with the duration of surgery. Moreover, the microbial cometabolites 3-hydroxyphenylpropionate, phenylacetylglycine, and hippurate correlated with the surgical insult, indicating that the gut microbiota are highly sensitive to the global homeostatic state of the host. Metabonomic profiling provides a global overview of surgical trauma that has the potential to provide novel biomarkers for personalized surgical optimization and outcome prediction.
  Journal of Proteome Research 01/2011; 10(1):277-87. · 5.11 Impact Factor
• Article: The human gut microbiome: implications for future health care.

  James M Kinross, Alexander C von Roon, Elaine Holmes, Ara Darzi, Jeremy K Nicholson
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  ABSTRACT: In their intestine, humans possess an "extended genome" of millions of microbial genes-the microbiome. Because this complex symbiosis influences host metabolism, physiology, and gene expression, it has been proposed that humans are complex biologic "superorganisms." Advances in microbiologic analysis and systems biology are now beginning to implicate the gut microbiome in the etiology of localized intestinal diseases such as the irritable bowel syndrome, inflammatory bowel disease, and colon cancer. These approaches also suggest possible links between the gut and previously unassociated systemic conditions such as type 2 diabetes and obesity. The elucidation of the intestinal microbiome is therefore likely to underpin future disease prevention strategies, personalized health care regimens, and the development of novel therapeutic interventions. This review summarizes the research that is defining our understanding of the intestinal microbiome and highlights future areas of research in gastroenterology and human health in which the intestinal microbiome will play a significant role.
  Current Gastroenterology Reports 08/2008; 10(4):396-403.