Protection of the Human Gut Microbiome From Antibiotics. (23rd November 2017)

• Record Type: Journal Article
• Authors: de Gunzburg, Jean; Ghozlane, Amine; Ducher, Annie; Le Chatelier, Emmanuelle; Duval, Xavier; Ruppé, Etienne; Armand-Lefevre, Laurence; Sablier-Gallis, Frédérique; Burdet, Charles; Alavoine, Loubna; Chachaty, Elisabeth; Augustin, Violaine; Varastet, Marina; Levenez, Florence; Kennedy, Sean; Pons, Nicolas; Mentré, France; Andremont, Antoine
• Is Part Of: Journal of infectious diseases. Volume 217:Number 4(2018)
• Page Start: 628
• Page End: 636
• Publication Date: 2017-11-23
• Subjects: microbiome -- antibiotics -- fluoroquinolones -- Clostridium difficile; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix604
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : In a phase 1 clinical study, coadministration of the adsorbent-based DAV132 product together with the fluoroquinolone antibiotic moxifloxacin, while not affecting the plasma concentrations of the antibiotic, reduced by >99% exposure of the intestinal microbiota to the moxifloxacin. Abstract: 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.