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Therapy of IBD: Identification of bacteria, bacterial components and the host intestinal immune mechanisms

Subject Area Parasitology and Biology of Tropical Infectious Disease Pathogens
Gastroenterology
Term from 2013 to 2018
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 237682965
 
The intestinal microbiota is a complex community of microorganisms that colonizes the gastrointestinal tract. Composition of the intestinal microbiota and number of microorganisms differs in dependency of the local environmental conditions. In previous work we showed that the commensal strain B. vulgatus is able to prevent and even more strikingly to heal IBD and that the bacterial factor promoting healing, prevention and even induction of IBD seems to be Lipid A, the bioactive part of LPS. The acylation and phosphorylation pattern of Lipid A seems to decide on an anti-inflammatory or pro-inflammatory effect. Therefore we will focus on two aspects, first the prerequisites of the host immune system and the microbes in healing IBD and second the interaction of therapeutic LPS with TLR4. We will analyze whether (i) the effect of B. vulgatus is a species or a strain specific effect, (ii) which cell type mediates healing of IBD by Bacteroides vulgatus/LPSBV, (iii) whether administration of LPSBV alters the composition of intestinal microbiota, (iv) the mechanisms of therapeutic LPS/TLR4 interaction, and (v) the intracellular processes mediating the antiinflammatory effect of B. vulgatus/LPSBV. The project will result in a deepened understanding of LPS/TLR4 interaction in IBD, the contribution to intestinal immune homeostasis and the potential of this interaction in restoring immune homoeostasis. Understanding the mechanisms and players influencing balance or imbalance of intestinal immune homoeostasis is essential for the development of novel therapeutics and therefore for new strategies in treatment of intestinal inflammatory disorders.
DFG Programme Priority Programmes
 
 

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