Medical Nutrition

We have multiple projects dericted at the potential of medical nutrition and specific probiotic ingredients to improve functional (EoE, IBS) or inflammatory gut diseases. It is increasingly evident that loss of immunological tolerance towards the intestinal microbiome contributes to the development of Inflammatory Bowel Diseases (IBD).

The gut bacteria attacking epithelial layers

Epithelial cells play a pivotal role in maintaining tolerance of the intestinal immune system. Hence strategies that fortify the tolerigenic properties of the epithelial layer may be efficacious in various inflammatory disorders, including IBD, as remission therapy. One of the advantages of targeting the epithelial layer is that it is at the mucosal surface and can therefore be efficiently modulated using food supplements or other forms of specialized nutrition. Therefore we aim to assay the true impact of shifts in metabolic activity of bacteria. A clear disadvantage of the use of clonal epithelial cell cultures (such as the commonly used Caco-2 or HT29 cell lines) is the fact that those are usually tumor cell derived and may not represent the full spectrum of specialized epithelial cells. Therefore we have adapted the crypt-organoid culture (mini-guts) in various research collaborative medical nutrition projects.

Figure 4A growth of enteroids with_without Butyrate

The mini-guts in a culture well

To allow study of the relevance of for instance Paneth cell function and antimicrobial peptide secretion, as well as epithelial responses to a changed probiotic or prebiotic influence and the metabolic consequences thereof. The Paneth cells amount up to 10% of the epithelial culture-all other relevant specialized epithelial cell types are represented such as neuroendocrine cells. Clearly, these crypt cell based organoid cultures have as advantage that all relevant epithelial cell types (i.e. Paneth cells) are fully represented in the culture. Our group at AMC, in collaboration with the Gastroenterology Department, is further exploring the possibility to adapt the human crypt cell cultures as described earlier at different levels and there is a clear opportunity for Gut Research partnering to test for instance probiotic products in this system.

This culture setup allows us to study the direct effects of pre- and probiotics but also microbial metabolic factors that regulate epithelial and Paneth cell peptide expression and secretion of antimicrobial peptides in an easily manipulated ex vivo setting. Further, we can study the effect of inflammatory cytokines that intervene in transcriptional regulation of antimicrobial peptide expression and secretion. Lentiviral shRNA strategies are in place to study specific gene regulation of epithelial responses.

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It is increasingly evident that loss of immunological tolerance towards the intestinal microbiome contributes to the development of Inflammatory Bowel Diseases (IBD).