Metagenomic changes in response to antibiotic treatment in severe orthopedic trauma patients
Afroditi Kouraki,
Amy S. Zheng,
Suzanne Miller,
Anthony Kelly,
Waheed Ashraf,
Davide Bazzani,
Angela Bonadiman,
Guendalina Tonidandel,
Mattia Bolzan,
Amrita Vijay,
Jessica Nightingale,
Cristina Menni,
Benjamin J. Ollivere,
Ana M. Valdes
Affiliations
Afroditi Kouraki
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK; Corresponding author
Amy S. Zheng
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
Suzanne Miller
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
Anthony Kelly
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
Waheed Ashraf
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
Davide Bazzani
Prebiomics srl, 38123 Trento, Italy
Angela Bonadiman
Prebiomics srl, 38123 Trento, Italy
Guendalina Tonidandel
Prebiomics srl, 38123 Trento, Italy
Mattia Bolzan
Prebiomics srl, 38123 Trento, Italy
Amrita Vijay
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
Jessica Nightingale
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
Cristina Menni
Department of Twin Research, King’s College London, London SE1 7EH, UK
Benjamin J. Ollivere
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
Ana M. Valdes
Academic Unit of Injury, Recovery and Inflammation Sciences, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham NG7 2UH, UK
Summary: We investigated changes in microbiome composition and abundance of antimicrobial resistance (AMR) genes post-antibiotic treatment in severe trauma patients. Shotgun sequencing revealed beta diversity (Bray-Curtis) differences between 16 hospitalized multiple rib fractures patients and 10 age- and sex-matched controls (p = 0.043), and between antibiotic-treated and untreated patients (p = 0.015). Antibiotic-treated patients had lower alpha diversity (Shannon) at discharge (p = 0.003) and 12-week post-discharge (p = 0.007). At 12 weeks, they also exhibited a 5.50-fold (95% confidence interval [CI]: 2.86–8.15) increase in Escherichia coli (p = 0.0004) compared to controls. Differential analysis identified nine AMRs that increased in antibiotic-treated compared to untreated patients between hospital discharge and 6 and 12 weeks follow-up (false discovery rate [FDR] < 0.20). Two aminoglycoside genes and a beta-lactamase gene were directly related to antibiotics administered, while five were unrelated. In trauma patients, lower alpha diversity, higher abundance of pathobionts, and increases in AMRs persisted for 12 weeks post-discharge, suggesting prolonged microbiome disruption. Probiotic or symbiotic therapies may offer future treatment avenues.
