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Protection of the human gut microbiome from antibiotics

View ORCID ProfileJean de Gunzburg, Amine Ghozlane, Annie Ducher, View ORCID ProfileEmmanuelle Le Chatelier, View ORCID ProfileXavier Duval, View ORCID ProfileEtienne Ruppé, Laurence Armand-Lefevre, Frédérique Sablier-Gallis, Charles Burdet, Loubna Alavoine, View ORCID ProfileElisabeth Chachaty, Violaine Augustin, Marina Varastet, Florence Levenez, View ORCID ProfileSean Kennedy, View ORCID ProfileNicolas Pons, View ORCID ProfileFrance Mentré, Antoine Andremont
doi: https://doi.org/10.1101/169813
Jean de Gunzburg
1Da Volterra, 75011 Paris, France
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  • ORCID record for Jean de Gunzburg
Amine Ghozlane
2Metagenopolis, INRA, 78532 Jouy-en-Josas, France
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Annie Ducher
1Da Volterra, 75011 Paris, France
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Emmanuelle Le Chatelier
2Metagenopolis, INRA, 78532 Jouy-en-Josas, France
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  • ORCID record for Emmanuelle Le Chatelier
Xavier Duval
3Bichat Claude Bernard Hospital, University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
4INSERM, IAME, UMR 1137, Paris, France; University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
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Etienne Ruppé
2Metagenopolis, INRA, 78532 Jouy-en-Josas, France
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  • ORCID record for Etienne Ruppé
Laurence Armand-Lefevre
3Bichat Claude Bernard Hospital, University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
4INSERM, IAME, UMR 1137, Paris, France; University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
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Frédérique Sablier-Gallis
1Da Volterra, 75011 Paris, France
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Charles Burdet
4INSERM, IAME, UMR 1137, Paris, France; University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
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Loubna Alavoine
3Bichat Claude Bernard Hospital, University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
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Elisabeth Chachaty
5Institut Gustave-Roussy, 94805 Villejuif, France.
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  • ORCID record for Elisabeth Chachaty
Violaine Augustin
1Da Volterra, 75011 Paris, France
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Marina Varastet
1Da Volterra, 75011 Paris, France
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Florence Levenez
2Metagenopolis, INRA, 78532 Jouy-en-Josas, France
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Sean Kennedy
2Metagenopolis, INRA, 78532 Jouy-en-Josas, France
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Nicolas Pons
2Metagenopolis, INRA, 78532 Jouy-en-Josas, France
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  • ORCID record for Nicolas Pons
France Mentré
4INSERM, IAME, UMR 1137, Paris, France; University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
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Antoine Andremont
3Bichat Claude Bernard Hospital, University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
4INSERM, IAME, UMR 1137, Paris, France; University Paris Diderot, Sorbonne Paris Cité, 75018 Paris, France
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ABSTRACT

Background Antibiotics are life-saving drugs but severely affect the gut microbiome with short term consequences including diarrhoea, Clostridium difficile infections and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers.

Methods We performed a randomized controlled trial (ClinicalTrials.gov NCT02176005) in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in two parallel groups, with or without DAV132 co-administration. Two control goups of 8 volunteers each receiving DAV132 alone, or a non-active substitute, were added.

Results The co-administration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex-vivo.

Conclusions DAV132 was highly effective to protect the gut microbiome of moxifloxacin - treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments.

Footnotes

  • Potential conflicts of interest: AD, FSG, VA and MV are employees of Da Volterra. JG, ER, CB, EC, FM and AA are consultants for Da Volterra. JG, AD, FSG and VA are shareholders of Da Volterra. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

  • Financial support: The randomised clinical trial was sponsored by Da Volterra (Paris) and funded in part by the European Union Seventh Framework Programme (FP7-HEALTH-2011-single-stage) under grant agreement n° 282004, EvoTAR. Additional funding was from the Metagenopolis grant ANR-11-DPBS-0001, and from BPIFrance under the NOSOBIO collaborative programme.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 04, 2017.
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Protection of the human gut microbiome from antibiotics
Jean de Gunzburg, Amine Ghozlane, Annie Ducher, Emmanuelle Le Chatelier, Xavier Duval, Etienne Ruppé, Laurence Armand-Lefevre, Frédérique Sablier-Gallis, Charles Burdet, Loubna Alavoine, Elisabeth Chachaty, Violaine Augustin, Marina Varastet, Florence Levenez, Sean Kennedy, Nicolas Pons, France Mentré, Antoine Andremont
bioRxiv 169813; doi: https://doi.org/10.1101/169813
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Protection of the human gut microbiome from antibiotics
Jean de Gunzburg, Amine Ghozlane, Annie Ducher, Emmanuelle Le Chatelier, Xavier Duval, Etienne Ruppé, Laurence Armand-Lefevre, Frédérique Sablier-Gallis, Charles Burdet, Loubna Alavoine, Elisabeth Chachaty, Violaine Augustin, Marina Varastet, Florence Levenez, Sean Kennedy, Nicolas Pons, France Mentré, Antoine Andremont
bioRxiv 169813; doi: https://doi.org/10.1101/169813

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