Probiotic Bacteria and the Gastrointestinal Barrier: miRNAs, Signaling Pathways and Molecular Repair Mechanisms

• Applicant: Professor Dr. Marcus Alexander Schmidt
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213208174

The intestinal ecosystem is characterized by a dynamic and balanced interaction between the resident microflora, the gastrointestinal barrier (GIB) and the (mucosal) immune system. In chronic inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn's disease, this balance is disturbed. Probiotic bacteria (e.g. E. coli Nissle 1917 (EcN) or lactobacilli) stabilize and/or regenerate the GIB by modulating intercellular junctions. However, the mechanisms underlying these effects are currently only poorly understood. This project aims at the elucidation of signaling pathways induced by Gram-negative and Gram-positive probiotics, the analysis of the relevant cellular targets in intestinal epithelial cells and in particular at cellular factors such as miRNAs involved in the regulation of barrier-relevant target structures. For probiotic bacteria, the responsible factors ('trigger factors') for the induction of signaling pathways are to be identified and characterized. Identification of microRNAs involved in the regulation of the epithelial barrier might potentially also provide new therapeutic applications. Therefore, as another aspect of this project the possible application of 'pre-miRNA' coupled to 'nanobeads', or alternatively ’ß1,3-D-glucan-encapsulated miRNA particles (GeRPs = ’yeast ghosts ’)’ or ’exosomes’ will be tested for potential application in a mouse model of IBD. For this, cell-penetrating peptides will also be employed for intracellular delivery.

• DFG Programme: Research Grants