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The role of intestinal microbiota in the development of inflammatory bowel diseases: identification of potential beneficial and harmful microbiota through ex vivo organoid technology.
The exact pathogenesis of inflammatory bowel diseases (IBD) remains incompletely understood, but a loss of tolerance to gut microbiota seems crucial. The differentiation of intestinal stem cells (ISC) into progeny cells is suggested to be disturbed in IBD, but the exact impact of microbiota on ISC is unknown. We hypothesize that ISC behave differently upon stimulation with luminal microbiota leading to altered differentiation into progeny, altered release of antimicrobial peptides by Paneth cells, and altered production of mucin by goblet cells. This hypothesis will be tested using an ex vivo long-term culture model. In this model, murine and human ISC will grow out into mini-guts containing all differentiated epithelial cell types (organoids). Next, the influence of microbiota on ISC behaviour and differentiation will be evaluated in a co-culture of such organoids in the presence of complete luminal microbiota, microbial proteins, or cell wall components.
Date:1 Oct 2014 → 30 Sep 2016
Keywords:Inflammatory bowel diseases, intestinal microbiota, ex vivo organoid technology., potential beneficial microbiota, potential harmful microbiota
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences