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严重骨科创伤患者对抗生素治疗的宏基因组变化

Metagenomic changes in response to antibiotic treatment in severe orthopedic trauma patients.

作者信息

Kouraki Afroditi, Zheng Amy S, Miller Suzanne, Kelly Anthony, Ashraf Waheed, Bazzani Davide, Bonadiman Angela, Tonidandel Guendalina, Bolzan Mattia, Vijay Amrita, Nightingale Jessica, Menni Cristina, Ollivere Benjamin J, Valdes Ana M

机构信息

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.

出版信息

iScience. 2024 Aug 22;27(9):110783. doi: 10.1016/j.isci.2024.110783. eCollection 2024 Sep 20.

Abstract

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 ( = 0.043), and between antibiotic-treated and untreated patients ( = 0.015). Antibiotic-treated patients had lower alpha diversity (Shannon) at discharge ( = 0.003) and 12-week post-discharge ( = 0.007). At 12 weeks, they also exhibited a 5.50-fold (95% confidence interval [CI]: 2.86-8.15) increase in ( = 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.

摘要

我们调查了严重创伤患者抗生素治疗后微生物组组成和抗菌药物耐药性(AMR)基因丰度的变化。鸟枪法测序显示,16例住院的多根肋骨骨折患者与10例年龄和性别匹配的对照之间存在β多样性(Bray-Curtis)差异(P = 0.043),抗生素治疗组与未治疗组之间也存在差异(P = 0.015)。抗生素治疗患者出院时(P = 0.003)和出院后12周(P = 0.007)的α多样性(Shannon)较低。在12周时,与对照组相比,他们的AMR也增加了5.50倍(95%置信区间[CI]:2.86-8.15)(P = 0.0004)。差异分析确定了9种AMR,在出院至随访6周和12周期间,抗生素治疗患者的AMR相比于未治疗患者增加(错误发现率[FDR]<0.20)。两个氨基糖苷类基因和一个β-内酰胺酶基因与所用抗生素直接相关,而另外五个则无关。在创伤患者中,较低的α多样性、致病共生菌的较高丰度以及AMR的增加在出院后持续12周,表明微生物组破坏持续时间较长。益生菌或共生菌疗法可能为未来的治疗提供途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcc2/11403444/9515dc9acd46/fx1.jpg

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