A toxic friend: Genotoxic and mutagenic activity of the probiotic strainEscherichia coliNissle 1917 Article Swipe
Jean‐Philippe Nougayrède
,
Camille V. Chagneau
,
Jean‐Paul Motta
,
Nadège Bossuet‐Greif
,
Marcy Belloy
,
Frédéric Taïeb
,
Jean‐Jacques Gratadoux
,
Muriel Thomas
,
Philippe Langella
,
Éric Oswald
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.03.22.436450
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.03.22.436450
The probiotic Escherichia coli strain 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 the pks pathogenicity 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 confirmed in vivo in 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. Importance Nissle 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 colibactin in vitro and in vivo and 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.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.03.22.436450
- https://www.biorxiv.org/content/biorxiv/early/2021/03/22/2021.03.22.436450.full.pdf
- OA Status
- green
- Cited By
- 2
- References
- 48
- Related Works
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- OpenAlex ID
- https://openalex.org/W3138487216
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3138487216Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2021.03.22.436450Digital Object Identifier
- Title
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A toxic friend: Genotoxic and mutagenic activity of the probiotic strainEscherichia coliNissle 1917Work title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
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2021-03-22Full publication date if available
- Authors
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Jean‐Philippe Nougayrède, Camille V. Chagneau, Jean‐Paul Motta, Nadège Bossuet‐Greif, Marcy Belloy, Frédéric Taïeb, Jean‐Jacques Gratadoux, Muriel Thomas, Philippe Langella, Éric OswaldList of authors in order
- Landing page
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https://doi.org/10.1101/2021.03.22.436450Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2021/03/22/2021.03.22.436450.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2021/03/22/2021.03.22.436450.full.pdfDirect OA link when available
- Concepts
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Probiotic, Biology, Escherichia coli, Gene, DNA damage, Microbiology, Colorectal cancer, DNA, Mutation, Carcinogenesis, Strain (injury), Genetics, Cancer, Bacteria, AnatomyTop concepts (fields/topics) attached by OpenAlex
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2Total citation count in OpenAlex
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2023: 1, 2021: 1Per-year citation counts (last 5 years)
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48Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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