Molecular interactions of mucosal tissues, bacteria and fibres
Project leader: Prof 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 project aimed 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 was investigated using advanced metagenomics-based molecular tools.
The insights generated in this project enables the definition of targeted dietary interventions for improved gastrointestinal health. In addition, the project delivered technology platform that allows monitoring of the effects of bacteria and/or fibres, and provided 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 were fractionated and modified using (microbial) enzymes or chemical modification, in order to study their bioactivity in more detail. This assisted in understanding of their structure-function relationship. Also, the degradation of products, during fermentation by the microbiota, was studied to evaluate the production of bioactive fibre-intermediates by human gut microbes and the sequential process of fibre degradation by the gut microbiota.