Metabolic Phenotyping in Health and Disease

Holmes, Elaine; Wilson, Ian D.; Nicholson, Jeremy K.

doi:10.1016/j.cell.2008.08.026

Cited by 727 publications

(591 citation statements)

References 14 publications

Supporting

Mentioning

578

Contrasting

Unclassified

Order By: Relevance

“…Gastric enzymes release the choline moiety from PC, and gut bacteria convert choline into TMA, which is then absorbed into the human body. Part of this TMA is then converted to TMAO by flavin-containing monooxygenases (FMOs) particularly by FMO3 (Holmes et al 2008) in the human body. While it is not immediately clear how exactly the genetic variation in PYROXD2 influences the amount of urine-secreted TMA, it seems that the metabolism of a precursor to a major metabolic marker for cardiovascular risk deserves further research.…”

Section: Holistic Metabolomics Phenotypes In Gwasmentioning

confidence: 99%

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

et al. 2012

View full text Add to dashboard Cite

Genome-wide association studies (GWASs) have become a very important tool to address the genetic origin of phenotypic variability, in particular associated with diseases. Nevertheless, these types of studies provide limited information about disease etiology and the molecular mechanisms involved. Recently, the incorporation of metabolomics into the analysis has offered novel opportunities for a better understanding of disease-related metabolic deregulation. The pattern emerging from this work is that gene-driven changes in metabolism are prevalent and that common genetic variations can have a profound impact on the homeostatic concentrations of specific metabolites. A particularly interesting aspect of this work takes into account interactions of environment and lifestyle with the genome and how this interaction translates into changes in the metabolome. For instance, the role of PY-ROXD2 in trimethylamine metabolism points to an interaction between host and microbiome genomes (host/ microbiota). Often, these findings reveal metabolic deregulations, which could eventually be tuned with a nutritional intervention. Here we review the development of gene-metabolism association studies from a single-gene/ single-metabolite to a genome-wide/metabolome-wide approach and highlight the conceptual changes associated with this ongoing transition. Moreover, we report some of our recent GWAS results on a cohort of 265 individuals from an ethnically diverse population that validate and refine previous findings on gene-urine metabolism interactions. Specifically, our results confirm the effect of PYROXD2 polymorphisms on trimethylamine metabolism and suggest that a previously reported association of N-acetylated compounds with the ALMS1/NAT8 locus is driven by SNPs in the ALMS1 gene.

show abstract

Section: Holistic Metabolomics Phenotypes In Gwasmentioning

confidence: 99%

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Metabolomics is a recently developed technology for detection, identification and quantification of low-molecularweight metabolites that are involved in the metabolism in an organism at a specified time under specific environmental conditions (11,12). this technique is an effective tool for Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity disease diagnosis (13)(14)(15), biomarker screening (16)(17)(18)(19)(20) and characterization of biological pathways (11).…”

Section: Introductionmentioning

confidence: 99%

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

Wang²,

Liu³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. the principal way to improve the outcome of gastric cancer (GC) is to predict carcinogenesis and metastasis at an early stage. the aims of the present study were to test the hypothesis that distinct metabolic profiles are reflected in GC tissues and to further explore potential biomarkers for GC diagnosis. Gas chromatography/mass spectrometry (GC/Ms) was utilized to analyze tissue metabolites from 30 GC patients. A diagnostic model for GC was constructed using orthogonal partial least squares discriminant analysis (OpLs-DA), and the metabolomic data were analyzed using the non-parametric Wilcoxon rank sum test to identify the metabolic tissue biomarkers for GC. Over 100 signals were routinely detected in one single total ion current (tIC) chromatogram, and the OPLS-DA model generated from the metabolic profile of the tissues adequately discriminated the GC tissues from the normal mucosae. Among the low-molecular-weight endogenous metabolites, a total of 41 compounds, such as amino acids, organic acids, carbohydrates, fatty acids and steroids, were detected, and 15 differential metabolites were identified with significant difference (p<0.05). A total of 20 variables were noted which contributed to a great extent in the discriminating OpLs-DA model (VIp value >1.0), among which 12 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test (p<0.05). In conclusion, the identification of the metabolites associated with GC morbidity potentially revealed perturbations of glycolysis, fatty acid β-oxidation, cholesterol and amino acid metabolism. these results suggest that tissue metabolic profiles have great potential in detecting GC and may aid in understanding its underlying mechanisms.

show abstract

“…A number of statistical tools can be employed to identify these metabotypes; some of the more common types include k-means analysis and hierarchical cluster analysis. In the field of personalised medicine, metabotyping may play a role by stratifying patients for the development of tailored healthcare solutions (45) . Examples of this concept are also available from the medical literature where cluster analysis has been used to identify different phenotypes for a range of diseases including chronic obstructive pulmonary disease (46) and Parkinsons disease (47) .…”

Section: Moving From Individuals To Groups: a Novel Use Of Phenotypinmentioning

confidence: 99%

Can metabotyping help deliver the promise of personalised nutrition?

et al. 2015

View full text Add to dashboard Cite

Over a decade since the completion of the human genome sequence, the promise of personalised nutrition available to all has yet to become a reality. While the definition was originally very gene-focused, in recent years, a model of personalised nutrition has emerged with the incorporation of dietary, phenotypic and genotypic information at various levels. Developing on from the idea of personalised nutrition, the concept of targeted nutrition has evolved which refers to the delivery of tailored dietary advice at a group level rather than at an individual level. Central to this concept is metabotyping or metabolic phenotyping, which is the ability to group similar individuals together based on their metabolic or phenotypic profiles. Applications of the metabotyping concept extend from the nutrition to the medical literature. While there are many examples of the metabotype approach, there is a dearth in the literature with regard to the development of tailored interventions for groups of individuals. This review will first explore the effectiveness of personalised nutrition in motivating behaviour change and secondly, examine potential novel ways for the delivery of personalised advice at a population level through a metabotyping approach. Based on recent findings from our work, we will demonstrate a novel strategy for the delivery of tailored dietary advice at a group level using this concept. In general, there is a strong emerging evidence to support the effectiveness of personalised nutrition; future work should ascertain if targeted nutrition can motivate behaviour change in a similar manner.

show abstract

Metabolic Phenotyping in Health and Disease

Cited by 727 publications

References 14 publications

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

Current status on genome–metabolome-wide associations: an opportunity in nutrition research

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

Can metabotyping help deliver the promise of personalised nutrition?

Contact Info

Product

Resources

About