Nutritional modulation of metabolic phenotypes

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Title: Nutritional modulation of metabolic phenotypes
Author(s): Heinzmann, Silke
Item Type: Thesis or dissertation
Abstract: Diet and other lifestyle factors play a critical role in the risk of developing many diseases. Metabolic profiles contain a wealth of biochemical and physiological information and are influenced by various factors such as gender, age, BMI or genetic background. Diet is an important factor, and long-term dietary habits as well as short-term food challenges influence the metabolic phenotype. Metabolic profiling technology can be used to discover novel single or combination biomarkers of food intake. To aid personalised healthy lifestyle recommendations, it is necessary to characterise the metabolic phenotype of individuals and to establish the extent to which we can beneficially influence this phenotype by nutritional intervention. This thesis aims to evaluate metabonomics as a tool for systematically detecting metabolites related to inter-individual and food-related differences. In order to address these aims a nutrition study was undertaken, where individuals followed a strict diet regime consuming a standard diet including specific food challenges, spot urine collections were made throughout the study period. 1H NMR spectroscopy was performed to generate urinary metabolic profiles, which were subsequently analysed and interpreted using multivariate mathematical modelling methods. Clear metabolic signatures pertaining to the consumption of specific dietary components and ‘biomarker’ metabolites associated with particular foods were extracted. Further validation of a potential biomarker was undertaken interrogating a large-scale epidemiologic dataset, the INTERMAP Study. Inter-individual variation in the metabolic profile was observed, both in relation to differences in response to food ingestion and metabolic differences independent from immediate food ingestion. Among these alterations were metabolites originating from gut microbial-mammalian co-metabolism. The influence of the gut microbiota on the metabolic phenotype and obesity was further investigated using microbially modulated murine models. This thesis characterises the effects of the interaction of diet and microbial metabolism on the metabolic phenotype and provides a template for assessing complex dietary interventions with respect to beneficially modulating metabolism.
Publication Date: 2010
Date Awarded: Feb-2011
URI: http://hdl.handle.net/10044/1/6320
Advisor: Nicholson, Jeremy
Holmes, Elaine
Sponsor/Funder: Nestle
Author: Heinzmann, Silke
Department: Surgery and Cancer
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses



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