The non-pathogenic<i>Escherichia coli</i>strain Nissle 1917 – features of a versatile probiotic

Probiotics are non-pathogenic living microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Probiotic microorganisms most often are constituents of special foodstuffs, such as fermented milk products or food supplements. They are also employed as feed additives in livestock breeding and as active components of medical remedies in human and veterinary medicine. In the food industry, probiotics traditionally are lactic acid bacteria (LAB), especially lactobacilli and lactococci, although bifidobacteria and strepcococci (enterococci) are also used. In livestock breeding and medicine, besides lactic acid bacteria other non-pathogenic microorganisms with health-promoting characteristics, e.g. certain strains of yeast (‘Saccharomyces boulardii’) and Escherichia coli (E. coli Nissle 1917), are also applied. This review focuses on the probiotic E. coli strain Nissle 1917 (EcN), its origin and medical history, microbiology, genetics, biological activities, safety, and toxicological aspects. Furthermore, clinical trials performed with this special E. coli strain will be summarized. The EcN strain was detected and isolated by Alfred Nissle in 1917 because of its antagonistic activity against some pathogenic entero-bacteria. With respect to its metabolic capacities, EcN is a typical E. coli strain. It is a non-pathogenic member of the Escherichia coli family, because it does does not carry pathogenic adhesion factors and does not produce any enterotoxins or cytotoxins, it is not invasive, not uropathogenic, and is rapidly killed by non-specific defense factors of blood serum. Besides this, EcN has some special characteristics that distinguish it from other pathogenic and non-pathogenic E. coli strains and are thought to be important for its probiotic activities. Thus, EcN carries so-called genomic islands (GEIs), integrated into its chromosome. On these GEIs, gene clusters coding for several fitness factors are present, e.g. genes for the production of microcins which inhibit the growth of other enterobacteria. Another strain-specific feature of EcN is a special lipopolysaccharide (LPS) in its outer cell membrane, being responsible for the fact that EcN exhibits immunomodulating properties without showing immunotoxic effects. The immunomodulating properties mainly focus on anti-inflammatory activities that are important for the clinical efficacy in remission maintenance of ulcerative colitis. Also of importance is the bacterial–epithelial crosstalk between EcN and the intestinal epithelial cells, leading to a strengthening of the epithelial barrier and the curing of ‘leaky gut’ phenomena. The restoration of a disturbed gut barrier by EcN is thought to be due to the stimulation of epithelial defensin production as well as to a ‘sealing effect’ on the tight junctions of the enterocytes. EcN has also been shown to induce the development of the gut immune system in animal models and human newborns. In addition, it has been found that products of EcN metabolism, probably acetic acid, promote colonic motility that might be helpful for therapeutic application in chronically constipated patients. Randomized controlled clinical trials (RCTs) have shown EcN to be therapeutically effective in rather diverse indications, such as ulcerative colitis, chronic constipation, and acute and protracted diarrhea.