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Final Activity Report Summary - GUTSYSTEM (Dietary Polyphenols, Gut Microbes and Human Health: A Systems Biology Approach)

Dietary polyphenols are plant molecules or metabolites that are abundantly present in our daily food including fruits, vegetables and beverages like tea. There are thousands of different polyphenol types. They can give the colour to red berries or the astringent taste to tea and wine. Dietary intake may reach up to 1 gram per day. Epidemiological studies suggest a link between polyphenol consumption and health. For example, three cups of green or black tea per day, which contains high levels of polyphenols, can lower your risk of stroke. Thus we know that polyphenols have an effect on our health. However, the mechanism of action of polyphenols is unclear and there is conflicting data for outcomes of polyphenol interventions. The technological and scientific challenges of gut microbiota-polyphenols interaction require a multi-disciplinary approach that was achieved in this project (GutSystem; 2006-2010).

The partners, University of Amsterdam (The Netherlands), University of Gent (Belgium) and INRA (France), contributed specific expertise, and the grant supported the secondments of 5 scientists for a total of 6 yrs. In our research we have studied the fate or journey of polyphenols in the human body with a multi-disciplinary approach. Initially, we used models of the human colon whereby the interaction of the polyphenols and colonic microbiota of different persons could be determined.

(1). The Simulator of the Human Intestinal Microbial Ecosystem, mimicking ascending, transverse and descending parts of the colon, provides access to microbial colonic fermentation without host interference. Marked alteration of the gut microbial diversity was observed as measured by modern molecular technologies including quantitative real time PCR and metagenomics of the 16S rRNA gene. Moreover, by developing and applying the latest metabolomics technologies, we showed that the gut microbes degraded the polyphenols to a range of smaller phenolic end products. Remarkably, each individuals gut microbiota degraded the polyphenols in a different manner.

The fate of the polyphenols in the human body was studied. Volunteers consumed polyphenols from black tea and red wine/grape extract and later the presence of the polyphenol derivatives from their blood and urine samples was measured using metabolomics. Typically the effects of polyphenols in interventions are small and confounded by factors such as background diet. Novel data analysis approaches to focus on the specific effect of the polyphenols was developed within the project, whereby we observed that each individual had a different pattern of polyphenol use which could differentiate human populations.

The uniqueness of their gut microbial composition is a significant factor in the different patterns (termed nutrikinetic phenotypes). These phenotypes may be responsible for conflicting outcomes in previous interventions and can be considered in future. A scheme for the fate of polyphenols in the human body is presented.

The determination of the fate of polyphenols within the human body described in this study will provide leads for involvement of specific polyphenolics in health benefits and improvement of these effects. Recently, the production of certain polyphenol metabolites could be correlated to specific gut microbial groups. Other research involves a metatranscriptomic approach to determine the impact of polyphenols on gut microbes and reveal bioconversion genes.

A platform for investigating host-microbiota-diet interactions using high throughput omics technologies and associated data analysis has been established by this project. The project team made numerous publications, presentations and one secondee received their PhD. In addition, comprehensive reviews on this subject upon invitation have been published in high impact prestigious journals such as PNAS USA.

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