NMC

Nutritional Metabolomics Project summaries

GUT AND IMMUNE HEALTH

The human gut microbiota has been recognized as a metabolically versatile digester playing an essential role in the regulation of the host metabolome. Non-digestible food components, in particular prebiotics, can modulate the microbial composition in the gut delivering health benefits to the host which may involve modulation of the immune system. The effect of non-digestible food components will be assessed in a human intervention study to find potential biomarkers and to generate novel hypotheses on gut and immune health. This study involves analysis on multiple levels (metabolomics, microbiome, immune modulators, transcriptomics) and in-vitro gut fermentation experiments. Metabolomic analysis (NMR/MS) will be applied on plasma, urine, faeces and in-vitro samples using state-of-the-art NMR- and MS-based profiling methods. Changes in these profiles will be assessed using multivariate statistical analysis, and these effects will be interpreted by pathway analysis.

DIET AND CARDIOMETABOLIC RISK

Diet and lifestyle are important determinants of cardiovascular disease (CVD) and type 2 diabetes (DM2). Major cardiometabolic risk factors, i.e. indicators of a person's risk of developing CVD or DM2, include elevated blood (LDL-) cholesterol and blood pressure (hypertension), and endothelial dysfunction and insulin resistance and impaired glycemic control. In this project metabolomics will be deployed to provide sensitive metabolic signatures that can establish the effect of dietary interventions on cardiometabolic health status and for early assessment of cardiometabolic risk. For this purpose dedicated nutritional intervention trials will be performed. The role of lipids will be explored using LCMS-based lipidomics approaches for low molecular weight lipid metabolites, and through NMR-based comprehensive serum lipoprotein analysis. Furthermore, LCMS-based profiling of inflammatory/vasodilation mediators will be undertaken, as well as profiling of metabolites related to oxidative and metabolic stress. Multivariate statistical analysis will be applied including thorough model validation to obtain biological interpretable metabolite patterns. Pathway Mapping software will be used to visualize changes in metabolic profiles on curated biochemical pathway maps. Modeling tools will be used to simulate/predict biological response and/or cardiometabolic risk.

DIET GUT INTERACTIONS: EFFECT OF FOOD FORMATS

Plants are a rich source of secondary metabolites (phytochemicals), which have been associated with enhancement of health and prevention of disease. A first step in explaining efficacy of a phytochemical is the demonstration of its bioavailability. This is a particular challenge, since phytochemicals mostly occur as complex mixtures, and/or are typically consumed within a dietary context. The implications on direct bioavailability are only partially understood and bioconversion by gut microbiota adds another level of complexity. Thus we need to be able to assess the phytochemical composition in different food formats during processing and shelf-life, as well as to understand the role of microbial diversity in making phytochemicals available from different food formats. A suite of phytochemical profiling platforms will be deployed (NMR, GCMS, LCMS) for assessment of effects of processing on phytochemical composition, effects of food format on bioconversion in vitro model experiments and in human intervention trials. These profiles will be subjected to multivariate statistical analysis including thorough model validation to obtain biological interpretable metabolite patterns. Data integration and fusion will be deployed to combine metabonomics with data on microbial diversity, followed by pathway analysis to interpret these (co)relations.

METABOLOMIC STUDIES ON THE EFFECT OF DIETARY INTERVENTIONS ON BODY WEIGHT AND BODY COMPOSITION

Obesity is a chronic disease, characterized by an excessive storage of body fat and is associated with many other illnesses, such as insulin resistance and cardiovascular disease. Furthermore, the greater morbidity among the elderly is associated with the progressive decline in skeletal muscle and function. The age-related loss of skeletal muscle mass is attributed to a disruption in the regulation of muscle protein turnover. This process is facilitated by a combination of factors, including a more sedentary lifestyle and a less than optimal diet. The underlying mechanisms controlling body weight and composition are complex and largely not understood, and holistic insight is required into the (sub-) population-specific responsiveness and effectiveness to food ingredients. Thus this project will exploit several long and short term dietary human intervention studies, including the EU DiOGenes trial (www.diogenes-eu.org ). In these studies body fluids are sampled for metabolic profiling, but also gene expression and anthropomorphic data are collected in order to finding metabolic signatures for the effect on weight loss and altered body fat distribution induced by energy restriction. Furthermore we aim at assessing the responsiveness of muscle protein synthesis to meal nutrients in particular proteins/peptides in elderly. For this purpose global metabolite profiling by NMR, GC- and LCMS will be carried out, as well as targeted profiling of low-molecular weight lipids (LCMS), lipoprotein distribution (NMR) and endocrines (LCMS). These profiles will be subjected to multivariate statistical analysis, including thorough model validation to obtain correlations between dietary interventions, metabolite patterns, gene expression and anthropomorphic changes. Metabolic pathway analysis will be carried out to interpret changes in metabolic signatures and effects on physiological endpoints.


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Nutritional Metabolomics Project summaries GUT AND IMMUNE HEALTH The human gut microbiota has been recognized as a metabolically versatile digester playing an essential role in the regulation of the host metabolome. Non-digestible food components, in particular prebiotics, can modulate the microbial composition in the gut delivering health benefits to the host which may involve modulation of the immune system. The effect of non-digestible food components will be assessed in a human intervention study to find potential biomarkers and to generate novel hypotheses on gut and immune health. This study involves analysis on multiple levels (metabolomics, microbiome, immune modulators, transcriptomics) and in-vitro gut fermentation experiments. Metabolomic analysis (NMR/MS) will be applied on plasma, urine, faeces and in-vitro samples using state-of-the-art NMR- and MS-based profiling methods. Changes in these profiles will be assessed using multivariate statistical analysis, and these effects will be interpreted by pathway analysis. DIET AND CARDIOMETABOLIC RISK Diet and lifestyle are important determinants of cardiovascular disease (CVD) and type 2 diabetes (DM2). Major cardiometabolic risk factors, i.e. indicators of a person's risk of developing CVD or DM2, include elevated blood (LDL-) cholesterol and blood pressure (hypertension), and endothelial dysfunction and insulin resistance and impaired glycemic control. In this project metabolomics will be deployed to provide sensitive metabolic signatures that can establish the effect of dietary interventions on cardiometabolic health status and for early assessment of cardiometabolic risk. For this purpose dedicated nutritional intervention trials will be performed. The role of lipids will be explored using LCMS-based lipidomics approaches for low molecular weight lipid metabolites, and through NMR-based comprehensive serum lipoprotein analysis. Furthermore, LCMS-based profiling of inflammatory/vasodilation mediators will be undertaken, as well as profiling of metabolites related to oxidative and metabolic stress. Multivariate statistical analysis will be applied including thorough model validation to obtain biological interpretable metabolite patterns. Pathway Mapping software will be used to visualize changes in metabolic profiles on curated biochemical pathway maps. Modeling tools will be used to simulate/predict biological response and/or cardiometabolic risk. DIET GUT INTERACTIONS: EFFECT OF FOOD FORMATS Plants are a rich source of secondary metabolites (phytochemicals), which have been associated with enhancement of health and prevention of disease. A first step in explaining efficacy of a phytochemical is the demonstration of its bioavailability. This is a particular challenge, since phytochemicals mostly occur as complex mixtures, and/or are typically consumed within a dietary context. The implications on direct bioavailability are only partially understood and bioconversion by gut microbiota adds another level of complexity. Thus we need to be able to assess the phytochemical composition in different food formats during processing and shelf-life, as well as to understand the role of microbial diversity in making phytochemicals available from different food formats. A suite of phytochemical profiling platforms will be deployed (NMR, GCMS, LCMS) for assessment of effects of processing on phytochemical composition, effects of food format on bioconversion in vitro model experiments and in human intervention trials. These profiles will be subjected to multivariate statistical analysis including thorough model validation to obtain biological interpretable metabolite patterns. Data integration and fusion will be deployed to combine metabonomics with data on microbial diversity, followed by pathway analysis to interpret these (co)relations. METABOLOMIC STUDIES ON THE EFFECT OF DIETARY INTERVENTIONS ON BODY WEIGHT AND BODY COMPOSITION Obesity is a chronic disease, characterized by an excessive storage of body fat and is associated with many other illnesses, such as insulin resistance and cardiovascular disease. Furthermore, the greater morbidity among the elderly is associated with the progressive decline in skeletal muscle and function. The age-related loss of skeletal muscle mass is attributed to a disruption in the regulation of muscle protein turnover. This process is facilitated by a combination of factors, including a more sedentary lifestyle and a less than optimal diet. The underlying mechanisms controlling body weight and composition are complex and largely not understood, and holistic insight is required into the (sub-) population-specific responsiveness and effectiveness to food ingredients. Thus this project will exploit several long and short term dietary human intervention studies, including the EU DiOGenes trial (www.diogenes-eu.org ). In these studies body fluids are sampled for metabolic profiling, but also gene expression and anthropomorphic data are collected in order to finding metabolic signatures for the effect on weight loss and altered body fat distribution induced by energy restriction. Furthermore we aim at assessing the responsiveness of muscle protein synthesis to meal nutrients in particular proteins/peptides in elderly. For this purpose global metabolite profiling by NMR, GC- and LCMS will be carried out, as well as targeted profiling of low-molecular weight lipids (LCMS), lipoprotein distribution (NMR) and endocrines (LCMS). These profiles will be subjected to multivariate statistical analysis, including thorough model validation to obtain correlations between dietary interventions, metabolite patterns, gene expression and anthropomorphic changes. Metabolic pathway analysis will be carried out to interpret changes in metabolic signatures and effects on physiological endpoints.		Life Sciences Momentum NGI The Hague, 23 November 2010 Johan Westerhuis receives EAS Award Amsterdam, March 2010 30th ISPPP - Call for Papers Bologna, Italy, 6-8 September 2010 NGI sponsors Postdoc Retreat The Hague, 21-23 April 2010 Pre-Seed Grant NGI The Hague, January 2010 Metabolomics in Nature's vision 2020 Nature Magazine 7 January 2010 Metabolomics receives first ever Impact Factor Rating UK 17 August 2009 NMC makes the difference NMC, Leiden Puzzling with metabolites NMC, NBIC, May 2009 First NMC paper published Amsterdam, Utrecht, January 2009 Robert Hall elected as secretary Metabolomics Society 11 December 2008

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