A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome

• Published in: Antimicrobial agents and chemotherapy Vol. 60; no. 7; pp. 4264 - 4273
• Main Authors: Yao, Jiangwei, Carter, Robert A., Vuagniaux, Grégoire, Barbier, Maryse, Rosch, Jason W., Rock, Charles O.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.07.2016
• Subjects: Animals; Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Experimental Therapeutics; Feces - microbiology; Female; Gastrointestinal Microbiome - drug effects; Mice; Mice, Inbred C57BL; Microbiota - drug effects; Microbiota - genetics; RNA, Ribosomal, 16S - genetics
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/AAC.00535-16

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.