Beschreibung:
<jats:title>ABSTRACT</jats:title><jats:p>Probiotics are viable microorganisms that are increasingly used for treatment of a variety of diseases. Occasionally, however, probiotics may have adverse clinical effects, including septicemia. Here we examined the role of the intestinal microbiota and the adaptive immune system in preventing translocation of probiotics (e.g.,<jats:italic>Escherichia</jats:italic><jats:italic>coli</jats:italic>Nissle). We challenged C57BL/6J mice raised under germfree conditions (GF-raised C57BL/6J mice) and<jats:italic>Rag1</jats:italic><jats:sup>−/−</jats:sup>mice raised under germfree conditions (GF-raised<jats:italic>Rag1</jats:italic><jats:sup>−/−</jats:sup>mice) and under specific-pathogen-free conditions (SPF-raised<jats:italic>Rag1</jats:italic><jats:sup>−/−</jats:sup>mice) with probiotic<jats:italic>E. coli</jats:italic>strain Nissle 1917, strain Nissle 1917 mutants, the commensal strain<jats:italic>E. coli</jats:italic>mpk, or<jats:italic>Bacteroides vulgatus</jats:italic>mpk. Additionally, we reconstituted<jats:italic>Rag1</jats:italic><jats:sup>−/−</jats:sup>mice with CD4<jats:sup>+</jats:sup>T cells.<jats:italic>E. coli</jats:italic>translocation and dissemination and the mortality of mice were assessed. In GF-raised<jats:italic>Rag1</jats:italic><jats:sup>−/−</jats:sup>mice, but not in SPF-raised<jats:italic>Rag1</jats:italic><jats:sup>−/−</jats:sup>mice or GF-raised C57BL/6J mice, oral challenge with<jats:italic>E. coli</jats:italic>strain Nissle 1917, but not oral challenge with<jats:italic>E. coli</jats:italic>mpk, resulted in translocation and dissemination. The mortality rate was significantly higher for<jats:italic>E. coli</jats:italic>strain Nissle 1917-challenged GF-raised<jats:italic>Rag1</jats:italic><jats:sup>−/−</jats:sup>mice (100%;<jats:italic>P</jats:italic>< 0.001) than for<jats:italic>E. coli</jats:italic>strain Nissle 1917-challenged SPF-raised<jats:italic>Rag1</jats:italic><jats:sup>−/</jats:sup><jats:sup>−</jats:sup>mice (0%) and GF-raised C57BL/6J mice (0%). Translocation of and mortality due to strain<jats:italic>E. coli</jats:italic>Nissle 1917 in GF-raised<jats:italic>Rag1</jats:italic><jats:sup>−/−</jats:sup>mice were prevented when mice were reconstituted with T cells prior to strain<jats:italic>E. coli</jats:italic>Nissle 1917 challenge, but not when mice were reconstituted with T cells after<jats:italic>E. coli</jats:italic>strain Nissle 1917 challenge. Cocolonization experiments revealed that<jats:italic>E. coli</jats:italic>mpk could not prevent translocation of strain<jats:italic>E. coli</jats:italic>Nissle 1917. Moreover, we demonstrated that neither lipopolysaccharide structure nor flagella play a role in<jats:italic>E. coli</jats:italic>strain Nissle 1917 translocation and dissemination. Our results suggest that if both the microbiota and adaptive immunity are defective, translocation across the intestinal epithelium and dissemination of the probiotic<jats:italic>E. coli</jats:italic>strain Nissle 1917 may occur and have potentially severe adverse effects. Future work should define the possibly related molecular factors that promote probiotic functions, fitness, and facultative pathogenicity.</jats:p>