Modulation of the gastrointestinal barrier function by probiotic Escherichia coli Nissle 1917

The effective use of probiotics in prevention and treatment of gastrointestinal and other infectious diseases has gained an increased relevance in the recent past. Beneficial effects of the probiotic E. coli Nissle 1917 (EcN) have been demonstrated by using this strain as therapeutic alternatives for the treatment of human inflammatory bowel diseases and intestinal disorders, but the molecular mechanisms behind its effect remain unclear. To investigate the effect of EcN on intestinal epithelial cells an in vitro as well as an in vivo model was established. A coculture system of human intestinal epithelial cell lines with probiotic EcN and control bacteria were used for whole genome expression analyses that were performed to identify a specific subset of EcN regulated human genes. Additionally, a bacterial colonization protocol of germ-free mice was established to analyse the in vivo impact of EcN on intestinal epithelial cells. These experimental systems together revealed an EcN specific up-regulation of genes coding on the one hand for immunological active proinflammatory molecules monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein-2 alpha (MIP-2 alpha) and macrophage inflammatory protein-2 beta (MIP-2 beta). Moreover, the gene coding for the tight junction protein ZO-1, a key molecule of the tight junctional complex, was also found to be up-regulated in intestinal epithelial cells after EcN exposure. Transfection of human intestinal epithelial cells with a ZO-1/GFP construct and subsequent infection experiments with enteropathogens demonstrated that overexpression of ZO-1 signifcantly reduced the infection rate. Thus, EcN might take part in the host defense process by establishing a protective immunological and physical barrier. Finally, these results may contribute to a better understanding of the beneficial effects of EcN and other probiotics, and support the development of optimized microorganisms for therapeutic use.