Commensal antimicrobial resistance mediates microbiome resilience to antibiotic disruption Journal Article


Authors: Bhattarai, S. K.; Du, M.; Zeamer, A. L.; M Morzfeld, B.; Kellogg, T. D.; Firat, K.; Benjamin, A.; Bean, J. M.; Zimmerman, M.; Mardi, G.; Vilbrun, S. C.; Walsh, K. F.; Fitzgerald, D. W.; Glickman, M. S.; Bucci, V.
Article Title: Commensal antimicrobial resistance mediates microbiome resilience to antibiotic disruption
Abstract: Despite their therapeutic benefits, antibiotics exert collateral damage on the microbiome and promote antimicrobial resistance. However, the mechanisms governing microbiome recovery from antibiotics are poorly understood. Treatment of Mycobacterium tuberculosis, the world's most common infection, represents the longest antimicrobial exposure in humans. Here, we investigate gut microbiome dynamics over 20 months of multidrug-resistant tuberculosis (TB) and 6 months of drug-sensitive TB treatment in humans. We find that gut microbiome dynamics and TB clearance are shared predictive cofactors of the resolution of TB-driven inflammation. The initial severe taxonomic and functional microbiome disruption, pathobiont domination, and enhancement of antibiotic resistance that initially accompanied long-term antibiotics were countered by later recovery of commensals. This resilience was driven by the competing evolution of antimicrobial resistance mutations in pathobionts and commensals, with commensal strains with resistance mutations reestablishing dominance. Fecal-microbiota transplantation of the antibiotic-resistant commensal microbiome in mice recapitulated resistance to further antibiotic disruption. These findings demonstrate that antimicrobial resistance mutations in commensals can have paradoxically beneficial effects by promoting microbiome resilience to antimicrobials and identify microbiome dynamics as a predictor of disease resolution in antibiotic therapy of a chronic infection.
Keywords: genetics; mouse; animal; animals; mice; antiinfective agent; antibiotic resistance; anti-bacterial agents; drug resistance, bacterial; intestine flora; microflora; microbiota; resilience, psychological; humans; human; psychological resilience; gastrointestinal microbiome
Journal Title: Science Translational Medicine
Volume: 16
Issue: 730
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2024-01-17
Start Page: eadi9711
Language: English
DOI: 10.1126/scitranslmed.adi9711
PUBMED: 38232140
PROVIDER: scopus
PMCID: PMC11017772
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Michael S. Glickman -- Source: Scopus
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MSK Authors
  1. James M Bean
    25 Bean
  2. Michael Glickman
    113 Glickman
  3. Muxue Du
    1 Du