Protection of the Human Gut Microbiome From Antibiotics

Jean de Gunzburg (1) , Amine Ghozlane (2) , Annie Ducher (1) , Emmanuelle Le Chatelier (2) , Xavier Marie Duval (3, 4, 5) , Etienne Ruppé (2) , Laurence Armand-Lefevre (4, 3, 5) , Frédérique Sablier-Gallis (1) , Charles Burdet (3) , Loubna Alavoine (4, 5) , Elisabeth Chachaty (6, 7) , Violaine Augustin (1) , Marina Varastet (1) , Florence Levenez (2) , Sean Kennedy (2) , Nicolas Pons (2) , France Mentré (3, 5) , Antoine Andremont (3, 5, 4)

1 Da Volterra [Paris, France]
2 MetaGenoPolis
3 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
4 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
5 Université Paris Diderot, Sorbonne Paris Cité, Paris, France
6 IGR - Institut Gustave Roussy
7 DSA - Département de soins aigus [Gustave Roussy]

Background: Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea 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 in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in 2 parallel groups, with or without DAV132 coadministration. Two control goups of 8 volunteers each receiving DAV132 alone, or a nonactive substitute, were added. Results: The coadministration 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. Clinical Trials Registration: NCT02176005.

Keywords: antibiotics; Clostridium difficile; microbiome; fluoroquinolones

Domains: Human health and pathology; Microbiology and Parasitology

Jean de Gunzburg, Amine Ghozlane, Annie Ducher, Emmanuelle Le Chatelier, Xavier Marie Duval, et al.. Protection of the Human Gut Microbiome From Antibiotics. Journal of Infectious Diseases, 2018, 217 (4), pp.628-636. ⟨10.1093/infdis/jix604⟩. ⟨pasteur-02552147⟩