E. coli strain Nissle 1917 strenghtens the ­intestinal barrier

Electron microscopic image: Intestinal epithelial cells with tight juncton sealling.

Tight junctions and certain desmosomes (adherence junctions) enable the cohesion of the intestinal epithelial cells. This phenomenon prevents the uncontrolled passage of substances from the intestines into the body (leaky gut-syndrome).

EcN enhances the expression of the tight-junction proteins zona occludens 1 and 2 and the desmosome protein named pinin, and thus stabilizes the intestinal barrier. 22; 26; 27

Interestingly, EcN is capable of reconstituting the tight junctions previously loosened by the attack of the enteropathogenic bacteria and thus reestablishing the integrity of the intestinal epithelium. As M. ­Alexander Schmidt and his colleagues working at the Institute of Infectiology of the University of Münster, Germany, were able to show by applying so-called DNA microarray technology, 22; 26 a co-incubation of intestinal epithelium cells (T84-cells) with EcN caused a time-dependent induction of gene expression for proteins which are involved in the structural make-up and integrity of the tight junctions and/or desmosomes. In summary, the contact between epithelial cells and EcN produced an alteration in the expression of more than 300 genes, whereby both an upregulation and downregulation of the gene activity of various epithelial hereditary factors has been determined. An increased gene expression of the tight junction proteins and/or desmosomal proteins ZO-2 and pinin was demonstrated in the T84-cells used, reaching a maximum after an incubation time of 120 minutes. 22

Further experiments conducted by the same working group 26 concerned with the molecular regulation of ZO-2-expression in epithelial cells were able to prove by applying high-resolution microscopic technology and specific fluorescence-labeled antibodies and protein-chemical analyses that EcN is capable of restoring an epithelial barrier previously destroyed by the infection with an enteropathogenic strain of E. coli (EPEC). In the course of this reaction the ZO-2-­protein is redistributed from the cytoplasm to the cell membrane of the epithelial cell. This stabilizing effect of EcN was reproduced in various cell culture experiments for both a prophylactic and a therapeutic ­applications.

Representation of the induction of ZO-2-gene expression in T84 epithelial cells and the incorporation of the ZO-2-protein into the tight junction. Staining with the ZO-2-specific fluorescent antibody shows (control without bacteria) that the ZO-2 protein is predominately localized in the membranes of the epithelium cells. This becomes evident by the strong light-red color of the cell contours. An incubation with E. coli strain Nissle 1917 (EcN) for 120-minutes did not alter the distribution of the ZO-2 protein. In contrast, a 120-minute incubation with an enteropathogenic E. coli strain (EPEC) induced a redistribution of ZO-2 and a reduction of the tightness of the tight junctions. In case of a concomitant incubation of EPEC and EcN the EPEC bacteria could not exhibit their noxious effects (after Zyrek et al., 2007).

Significance for the clinical practice

As a consequence for the clinical practice, it follows from these experimental results that the E. coli strain Nissle 1917 is capable of strengthening and regene­rating the intestinal barrier function.
This may be of central significance to the efficacy of EcN in various gastroenterological, hepatological and allergological-immunological diseases, which are associated with the “leaky gut-phenomena” and are caused by the increased permeability of the intestinal epithelium.

22) Cichon C et al. DNA-Microarray-based comparison of cellular responses in polarized T84 epithelial cells triggered by probiotics: E. coli Nissle 1917 (EcN) and Lactobacillus ­aci­dophilus PZ1041. Gastroenterology 2004; 126(4): A-578.

26) Zyrek AA et al. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCz redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol 2007; 9: 804–816.

27) Ukena SN et al. Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing ­mucosal integrity. PLOS ONE 2007; 12: e1308; 1–9.

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