Brief antibiotic use drives human gut bacteria towards low-cost resistance

Eitan Yaffe (), Les Dethlefsen, Arati V. Patankar, Chen Gui, Susan Holmes and David A. Relman
Additional contact information
Eitan Yaffe: Stanford University School of Medicine
Les Dethlefsen: Stanford University School of Medicine
Arati V. Patankar: Veterans Affairs Palo Alto Health Care System
Chen Gui: Veterans Affairs Palo Alto Health Care System
Susan Holmes: Stanford University
David A. Relman: Stanford University School of Medicine

Nature, 2025, vol. 641, issue 8061, 182-191

Abstract: Abstract Understanding the relationship between antibiotic use and the evolution of antimicrobial resistance is vital for effective antibiotic stewardship. Yet, animal models and in vitro experiments poorly replicate real-world conditions1. To explain how resistance evolves in vivo, we exposed 60 human participants to ciprofloxacin and used longitudinal stool samples and a new computational method to assemble the genomes of 5,665 populations of commensal bacterial species within participants. Analysis of 2.3 million polymorphic sequence variants revealed 513 populations that underwent selective sweeps. We found convergent evolution focused on DNA gyrase and evidence of dispersed selective pressure at other genomic loci. Roughly 10% of susceptible bacterial populations evolved towards resistance through sweeps that involved substitutions at a specific amino acid in gyrase. The evolution of gyrase was associated with large populations that decreased in relative abundance during exposure. Sweeps persisted for more than 10 weeks in most cases and were not projected to revert within a year. Targeted amplification showed that gyrase mutations arose de novo within the participants and exhibited no measurable fitness cost. These findings revealed that brief ciprofloxacin exposure drives the evolution of resistance in gut commensals, with mutations persisting long after exposure. This study underscores the capacity of the human gut to promote the evolution of resistance and identifies key genomic and ecological factors that shape bacterial adaptation in vivo.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-025-08781-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:641:y:2025:i:8061:d:10.1038_s41586-025-08781-x

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-025-08781-x

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().