Impact of selective digestive decontamination on patient gut microbiome. gut metagenome

To study the effect of antibiotic therapy during patient hospitalization on the antibiotic resistance gene (ARG) reservoir (‘the resistome’) formed by the human microbiota, conventional clinical culturing methods are insufficient. Here, we apply functional metagenomics (using large-insert fosmid libraries in Escherichia coli) and metagenomic shotgun sequencing to examine resistome dynamics in a patient admitted to an Intensive Care Unit, throughout hospital stay and nine months after hospital discharge. Our data indicate that selection for antibiotic resistance, specifically among anaerobic gut commensals, occurs during hospital stay. Functional metagenomics provided data on the genetic context of the resistance genes, which are frequently associated with putative mobile genetic elements. Metagenomic sequencing allowed the identification and relative quantification of many ARGs (between one and eleven for each antibiotic family) per sampled time-point. We suggest that metagenomic shotgun sequencing may be applied as a monitoring tool to detect and quantify ARGs in patient microbiota.

为探究患者住院期间的抗生素治疗对人体菌群所形成的抗生素抗性基因(antibiotic resistance gene, ARG)库（又称抗性组(resistome)）产生的影响，传统临床培养方法存在局限性。本研究采用功能宏基因组学(functional metagenomics，以大肠杆菌(Escherichia coli)构建大片段fosmid文库(large-insert fosmid libraries))与宏基因组鸟枪测序法(metagenomic shotgun sequencing)，对一名入住重症监护病房(Intensive Care Unit, ICU)的患者，在其整个住院期间及出院后九个月内的肠道抗性组动态变化进行分析。研究数据显示，抗生素抗性的筛选过程（尤其在肠道厌氧共生菌(anaerobic gut commensals)中）发生于住院期间。功能宏基因组学可提供抗性基因的遗传背景信息，这类基因常与推定的可移动遗传元件(mobile genetic elements)相关联。宏基因组测序则可实现每个采样时间点下多种ARG的鉴定与相对定量，每种抗生素类别对应1至11个ARG。本研究提示，宏基因组鸟枪测序法可作为监测工具，用于检测并定量患者菌群中的抗生素抗性基因。