A Toxic Friend: Genotoxic and Mutagenic Activity of the Probiotic Strain Escherichia coli Nissle 1917

Autor: Eric Oswald, Marcy Belloy, Nadège Bossuet-Greif, Jean-Philippe Nougayrède, Jean-Paul Motta, Camille V. Chagneau, Jean-Jacques Gratadoux, Frédéric Taieb, Philippe Langella, Muriel Thomas
Přispěvatelé: Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National Du Cancer (INCA PLBIO13-123), European Project: 609398,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,AGREENSKILLSPLUS(2014), SEGUIN, Nathalie, AgreenSkills+ - AGREENSKILLSPLUS - - EC:FP7:PEOPLE2014-05-05 - 2019-05-04 - 609398 - VALID, CHU Toulouse [Toulouse], Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
DNA damage
Mutaflor
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain
Biology
Gene mutation
medicine.disease_cause
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Microbiology
law.invention
03 medical and health sciences
Probiotic
[SDV.CAN] Life Sciences [q-bio]/Cancer
In vivo
law
medicine
Escherichia coli
genotoxin
Gene
030304 developmental biology
0303 health sciences
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
030306 microbiology
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
Pathogenicity island
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
QR1-502
3. Good health
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
[SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain
nervous system
[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
colibactin
probiotic
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Research Article
Zdroj: MSphere
MSphere, American Society for Microbiology., 2021, 6 (4), 11 p. ⟨10.1128/mSphere.00624-21⟩
MSphere, 2021, 6 (4), 11 p. ⟨10.1128/mSphere.00624-21⟩
mSphere, Vol 6, Iss 4 (2021)
mSphere
ISSN: 2379-5042
Popis: The probioticEscherichia colistrain Nissle 1917 (DSM 6601, Mutaflor), generally considered as beneficial and safe, has been used for a century to treat various intestinal diseases. However, Nissle 1917 hosts in its genome thepkspathogenicity island that codes for the biosynthesis of the genotoxin colibactin. Colibactin is a potent DNA alkylator, suspected to play a role in colorectal cancer development. We show in this study that Nissle 1917 is functionally capable of producing colibactin and inducing interstrand crosslinks in the genomic DNA of epithelial cells exposed to the probiotic. This toxicity was even exacerbated with lower doses of the probiotic, when the exposed cells started to divide again but exhibited aberrant anaphases and increased gene mutation frequency. DNA damage was confirmedin vivoin mouse models of intestinal colonization, demonstrating that Nissle 1917 produces the genotoxin in the gut lumen. Although it is possible that daily treatment of adult humans with their microbiota does not produce the same effects, administration of Nissle 1917 as a probiotic or as a chassis to deliver therapeutics might exert long term adverse effects and thus should be considered in a risk versus benefit evaluation.ImportanceNissle 1917 is sold as a probiotic and considered safe even though it is known since 2006 that it encodes the genes for colibactin synthesis. Colibactin is a potent genotoxin that is now linked to causative mutations found in human colorectal cancer. Many papers concerning the use of this strain in clinical applications ignore or elude this fact, or misleadingly suggest that Nissle 1917 does not induce DNA damage. Here, we demonstrate that Nissle 1917 produces colibactinin vitroandin vivoand induces mutagenic DNA damage. This is a serious safety concern that must not be ignored, for the interests of patients, the general public, health care professionals and ethical probiotic manufacturers.
Databáze: OpenAIRE
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