Microbial diversity and antimicrobial resistance in faecal samples from acute medical patients assessed through metagenomic sequencing.

Microbial diversity and antimicrobial resistance in faecal samples from acute medical patients assessed through metagenomic sequencing.
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DOI:
10.1371/journal.pone.0282584
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发表时间:
2023
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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抗菌素耐药性(AMR)是对全球公共健康的威胁。然而,直接衡量个人承担的老年保健费用负担的方法不令人满意,阻碍了评估旨在减少选择老年保健费用的干预措施的努力。元基因组学可以准确地检测和量化个人粪便菌群(他们的肠道“抵抗组”)中的AMR基因。使用这种方法,我们的目的是检验这样一个假设,即英国不同医院之间抗菌剂使用的差异将导致个别患者的耐药性明显不同。三个抗生素使用和艰难梭状芽孢杆菌感染率明显不同的国家卫生服务急性医院信托基金收集了匿名患者的粪便样本,这些样本在艰难梭菌检测后9至15个月内被丢弃。从这些样品中提取后基因组DNA,并使用Illumina NovaSeq 6000平台进行测序。对所得的测序读数进行分类组成和AMR基因的存在分析。在683个粪便元基因组中,我们发现个体之间在分类多样性(Shannon Index范围0.10-3.99)和AMR基因携带量(中位数1.50基因/细胞/样本)方面存在巨大差异。我们发现,三个信托基金在多样性(Shannon指数中位数2.16(IQR 1.71-2.56)、2.15(IQR 1.62-2.50)和2.26(IQR 1.55-2.51))或AMR基因携带量(中位数1.37基因/细胞/样本(IQR 0.70-3.24)、1.70(IQR 0.70-4.52)和1.43(IQR 0.55-3.71))方面没有统计学差异。在信托基金的整个样本采集期内也是如此。虽然我们还没有使用粪便废物的元基因组测序来证明不同地点或时间的差异,但其他采样框架可能更适合于确定抗生素使用的组织水平差异是否与AMR携带负担的个人水平差异相关。
Antimicrobial resistance (AMR) is a threat to global public health. However, unsatisfactory approaches to directly measuring the AMR burden carried by individuals has hampered efforts to assess interventions aimed at reducing selection for AMR. Metagenomics can provide accurate detection and quantification of AMR genes within an individual person’s faecal flora (their gut “resistome”). Using this approach, we aimed to test the hypothesis that differences in antimicrobial use across different hospitals in the United Kingdom will result in observable differences in the resistome of individual patients. Three National Health Service acute Hospital Trusts with markedly different antibiotic use and Clostridioides difficile infection rates collected faecal samples from anonymous patients which were discarded after C. difficile testing over a period of 9 to 15 months. Metagenomic DNA was extracted from these samples and sequenced using an Illumina NovaSeq 6000 platform. The resulting sequencing reads were analysed for taxonomic composition and for the presence of AMR genes. Among 683 faecal metagenomes we found huge variation between individuals in terms of taxonomic diversity (Shannon Index range 0.10–3.99) and carriage of AMR genes (Median 1.50 genes/cell/sample overall). We found no statistically significant differences in diversity (median Shannon index 2.16 (IQR 1.71–2.56), 2.15 (IQR 1.62–2.50) and 2.26 (IQR 1.55–2.51)) or carriage of AMR genes (median 1.37 genes/cell/sample (IQR 0.70–3.24), 1.70 (IQR 0.70–4.52) and 1.43 (IQR 0.55–3.71)) at the three trusts respectively. This was also the case across the sample collection period within the trusts. While we have not demonstrated differences over place or time using metagenomic sequencing of faecal discards, other sampling frameworks may be more suitable to determine whether organisational level differences in antibiotic use are associated with individual-level differences in burden of AMR carriage.
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