FORIMMUN

RESEARCH NETWORK FOR NEW STRATEGIES IN IMMUNOTHERAPY

M1 M1 - Molecular Mechanisms in Immuntherapy of Digestive Tract Diseases Caused by Bacteria

Research issues:
Probiotics are applied internationally with increasing frequency for therapy and prophylaxis in various diseases. Probiotic microorganisms are able to modulate a host’s immune response. The probiotic Escherichia coli strain Nissle1917 (EcN) is employed as a model to elucidate the responsible molecular mechanisms. Genetic techniques will help to develop strategies for improvement of the probiotic ability of this strain. These studies include the use of human epithelial cells of the digestive tract, the mouse as an animal model and the DNA-chip technology. One aim is to prove the safety of EcN scientifically by demonstrating the absence of virulence genes, i.e. lack of genetic determinants essential for causing disease. This is achieved by the current analysis of the EcN genome.

Results:
An important property regarding EcN’s probiotic effect is - among other things - the production of microcins. These compounds are able to kill other bacteria, also pathogenic ones. In addition, we could demonstrate with human gut epithelial cell lines that EcN inhibits cell invasion by various enteropathogenic bacteria. This anti-invasive activity of EcN might strengthen the barrier function of the gut mucosa by EcN in humans treated with this bacterium. In turn, this could help to protect against disease caused by enteropathogenic bacteria as salmonellae. From future experiments we expect further interesting results allowing to draw conclusions about the role of genes and their products from the Nissle 1917 strain as well as the host cells (human, mouse) involved in immune modulation directed by this probiotic microorganism.

Application:
The probiotic E. coli strain Nissle1917 is the effective ingredient of the drug "Mutaflor". Mutaflor is an already established therapeutic with proven clinical effectivity. However, the mechanisms of action are not yet deciphered. The elucidation of the mechanisms of action exerted by this strain and optimizing its probiotic nature will increase its medical attraction.