title: A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome.
abstract: Broad-spectrum antibiotic therapy decimates the gut microbiome, resulting in a variety of negative health consequences. Debio 1452 is a staphylococcus-selective enoyl-acyl carrier protein reductase (FabI) inhibitor under clinical development and was used to determine whether treatment with pathogen-selective antibiotics would minimize disturbance to the microbiome. The effect of oral Debio 1452 on the microbiota of mice was compared to the effects of four commonly used broad-spectrum oral antibiotics. During the 10 days of oral Debio 1452 treatment, there was minimal disturbance to the gut bacterial abundance and composition, with only the unclassified S24-7 taxon reduced at days 6 and 10. In comparison, broad-spectrum oral antibiotics caused ∼100- to 4,000-fold decreases in gut bacterial abundance and severely altered the microbial composition. The gut bacterial abundance and composition of Debio 1452-treated mice were indistinguishable from those of untreated mice 2 days after the antibiotic treatment was stopped. In contrast, the bacterial abundance in broad-spectrum-antibiotic-treated mice took up to 7 days to recover, and the gut composition of the broad-spectrum-antibiotic-treated mice remained different from that of the control group 20 days after the cessation of antibiotic treatment. These results illustrate that a pathogen-selective approach to antibiotic development will minimize disturbance to the gut microbiome.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Jiangwei
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Carter
authors.affiliation: Debiopharm International SA, Lausanne, Switzerland.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Vuagniaux
authors.affiliation: Debiopharm International SA, Lausanne, Switzerland.
authors.forename: Maryse
authors.initials: M
authors.lastname: Barbier
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Rosch
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA charles.rock@stjude.org.
authors.forename: Charles O
authors.initials: CO
authors.lastname: Rock
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S