Influence of microbiota on intestinal stem cell behavior, differentiation and migration in patients with inflammatory bowel disease.

The exact pathogenesis of Crohns disease (CD) remains incompletely understood, but a loss of tolerance to normal gut microbes seems crucial. Interactions between host and microbes take place at the intestinal surface which exists of enterocytes, goblet, entero-endocrine and Paneth cells. All these cells arise from crypt-based intestinal stem cells (ISC) and are renewed constantly. The impact of bacteria on ISC has not been explored yet. We hypothesize that ISC behave differently after stimulation with luminal microbiota leading to altered differentiation into progeny and altered release of anti-microbial peptides by Paneth cells. ISC behavior will be compared between tissue samples from CD patients (active or inactive disease) and controls by evaluating specific markers of ISC and their progeny. Furthermore, these markers will be evaluated in a murine and human intestinal culture, including ISC which are able to differentiate in vitro, after incubation with pro-inflammatory (Escherichia coli) or anti-inflammatory microbes (Faecalibacterium prausnitzii). Findings will be confirmed in cultures with one cell type (ISC, enterocytes, ) and in co-cultures with dentritic cells, which play a role in directing the immune response against intestinal microbes. Finally, mice will be infected with these microbes to evaluate the influence on the aforementioned markers in vivo.

Keywords:Microbiotica, Differentiation, Behavior, Paneth cell, Intestinal epithelium, Intestinal stem cell, Crohn's disease, Inflammatory Bowel diseases, Microbiota

Disciplines:Laboratory medicine, Gastro-enterology and hepatology, Immunology