Molecular interactions

koen venema 90

Project leader: Dr Koen Venema
Time Frame: 2011 – 2015
Project code: GH004
Project login (project members only)




To date, there is little understanding of the mechanisms underlying interactions between intestinal bacteria, dietary components and intestinal-mucosa function. This hampers the development of targeted dietary interventions to improve gastrointestinal health. The Molecular interactions project aims to provide mechanistic insights into the communication between generic bacterial components of gram-positive, cell-wall constituents and epithelial, immune and endocrine cells in the intestinal mucosa. In addition, a number of dietary oligosaccharides and polysaccharides (fibres) have been selected to evaluate their potential in direct signalling with mucosal tissues. Moreover, the impact of these fibres on the in situ metabolism of the microbiota is being investigated using advanced metagenomics-based molecular tools.

The insights generated in this project will enable the definition of targeted dietary interventions for improved gastrointestinal health. In addition, the project will provide a technology platform that allows monitoring of the effects of bacteria and/or fibres, and will provide tools for determining compositional and functional changes within the intestinal microbiota.

Assays of immune-system cells and also reporter cells, that study signalling through different pattern-recognition receptors, were used to screen a number of mutants of the probiotic L. plantarum WCFS1. These mutants were devoid of several major cell-wall components, such as lipoteichoic- and wall-teichoic acid, lipoproteins, and/or glycosylated proteins. In addition, the effect of a collection of >50 fibres on immune cells was analysed. This led to ongoing characterisation of a number of relevant mutants and fibres. For example, active fibre preparations are fractionated and modified using (microbial) enzymes or chemical modification, in order to study their bioactivity in more detail. This should lead to an understanding of their structure-function relationship. Also, the degradation of products, during fermentation by the microbiota, is being studied to evaluate the production of bioactive fibre-intermediates by human gut microbes and the sequential process of fibre degradation by the gut microbiota.



Recent publications

Scientific papers in peer-reviewed journals 2015 The art of targeting gut microbiota for tackling human obesity View summary
Scientific papers in peer-reviewed journals 2015 Evaluation of an optimal preparation of human faecal inocula for in vitro fermentation studies View summary
Scientific papers in peer-reviewed journals 2015 The use of fecal samples for studying human obesity View summary
Scientific papers in peer-reviewed journals 2016 Diet drives quick changes in the metabolic activity and composition of human gut microbiota in a validated in vitro gut model View summary