Safety of Probiotic
Escherichia coli
Strain Nissle 1917 Depends on Intestinal Microbiota and Adaptive Immunity of the Host
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Published:2010-07
Issue:7
Volume:78
Page:3036-3046
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ISSN:0019-9567
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Container-title:Infection and Immunity
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language:en
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Short-container-title:Infect Immun
Author:
Gronbach Kerstin1, Eberle Ute1, Müller Martina1, Ölschläger Tobias A.2, Dobrindt Ulrich2, Leithäuser Frank3, Niess Jan Hendrik4, Döring Gerd1, Reimann Jörg4, Autenrieth Ingo B.1, Frick Julia-Stefanie1
Affiliation:
1. Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany 2. Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany 3. Department of Pathology 4. Department of Internal Medicine I, University of Ulm, Ulm, Germany
Abstract
ABSTRACT
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.,
Escherichia
coli
Nissle). We challenged C57BL/6J mice raised under germfree conditions (GF-raised C57BL/6J mice) and
Rag1
−/−
mice raised under germfree conditions (GF-raised
Rag1
−/−
mice) and under specific-pathogen-free conditions (SPF-raised
Rag1
−/−
mice) with probiotic
E. coli
strain Nissle 1917, strain Nissle 1917 mutants, the commensal strain
E. coli
mpk, or
Bacteroides vulgatus
mpk. Additionally, we reconstituted
Rag1
−/−
mice with CD4
+
T cells.
E. coli
translocation and dissemination and the mortality of mice were assessed. In GF-raised
Rag1
−/−
mice, but not in SPF-raised
Rag1
−/−
mice or GF-raised C57BL/6J mice, oral challenge with
E. coli
strain Nissle 1917, but not oral challenge with
E. coli
mpk, resulted in translocation and dissemination. The mortality rate was significantly higher for
E. coli
strain Nissle 1917-challenged GF-raised
Rag1
−/−
mice (100%;
P
< 0.001) than for
E. coli
strain Nissle 1917-challenged SPF-raised
Rag1
−/
−
mice (0%) and GF-raised C57BL/6J mice (0%). Translocation of and mortality due to strain
E. coli
Nissle 1917 in GF-raised
Rag1
−/−
mice were prevented when mice were reconstituted with T cells prior to strain
E. coli
Nissle 1917 challenge, but not when mice were reconstituted with T cells after
E. coli
strain Nissle 1917 challenge. Cocolonization experiments revealed that
E. coli
mpk could not prevent translocation of strain
E. coli
Nissle 1917. Moreover, we demonstrated that neither lipopolysaccharide structure nor flagella play a role in
E. coli
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
E. coli
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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