Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome.

Developmental dynamics of the preterm infant gut microbiota and antibiotic resistome.
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早产儿肠道菌群和抗生素耐药组的发育动力学。

DOI:
10.1038/nmicrobiol.2016.24
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发表时间:
2016-03-07
影响因子:
28.3
通讯作者:
Dantas, Gautam
Dantas, Gautam
中科院分区:
生物学1区
文献类型:
--
作者:
Gibson, Molly K.;Wang, Bin;Ahmadi, Sara;Burnham, Carey-Ann D.;Tarr, Phillip I.;Warner, Barbara B.;Dantas, Gautam

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早产儿肠道微生物群的发展正在成为一个关键的研究重点。由于早产儿几乎普遍接受早期且通常延长的抗生素治疗,因此了解这些干预措施如何改变肠道微生物群发育非常重要。对84例纵向采样早产儿的401份粪便进行分析,结果表明美罗培南、头孢噻肟和替卡西林-克拉维酸与物种丰富度显著降低相关。相比之下,万古霉素和庆大霉素,最常给予早产儿的抗生素,对物种丰富度的影响不一致,但这些可以预测85%的准确度的基础上,只有两个细菌物种和两个抗生素耐药(AR)基因在治疗开始的相对丰度。为了研究耐药基因组的发展,我们从21个粪便宏基因组表达文库中功能性地选择了对16种抗生素的耐药性。在鉴定的794个AR基因中,79%以前未被归类为AR基因。结合对所有粪便的深度鸟枪测序,我们发现,通常与医院感染相关的埃希氏菌属、克雷伯氏菌属和肠杆菌属的多药耐药成员在早产儿肠道菌群中占主导地位。在特定抗生素治疗后富集的AR基因通常是特定治疗所特有的,并且与单个物种的丰度高度相关。最显著的例外包括替卡西林-克拉维西林和氨苄西林,两者都富集大量重叠AR基因,并且与肺炎克雷伯氏菌相关。我们发现,所有抗生素治疗都与广泛的附带微生物组影响有关,这是通过富集对特定抗生素驱动因子没有已知活性的AR基因来实现的。
Development of the preterm infant gut microbiota is emerging as a critical research priority. Since preterm infants almost universally receive early and often extended antibiotic therapy, it is important to understand how these interventions alter gut microbiota development. Analysis of 401 stools from 84 longitudinally sampled preterm infants demonstrates that meropenem, cefotaxime and ticarcillin–clavulanate are associated with significantly reduced species richness. In contrast, vancomycin and gentamicin, the antibiotics most commonly administered to preterm infants, have non-uniform effects on species richness, but these can be predicted with 85% accuracy based on the relative abundance of only two bacterial species and two antibiotic resistance (AR) genes at treatment initiation. To investigate resistome development, we functionally selected resistance to 16 antibiotics from 21 faecal metagenomic expression libraries. Of the 794 AR genes identified, 79% had not previously been classified as AR genes. Combined with deep shotgun sequencing of all stools, we find that multidrug-resistant members of the genera Escherichia, Klebsiella and Enterobacter, genera commonly associated with nosocomial infections, dominate the preterm infant gut microbiota. AR genes that are enriched following specific antibiotic treatments are generally unique to the specific treatment and are highly correlated with the abundance of a single species. The most notable exceptions include ticarcillin–clavulanate and ampicillin, both of which enrich for a large number of overlapping AR genes, and are correlated with Klebsiella pneumoniae. We find that all antibiotic treatments are associated with widespread collateral microbiome impact by enrichment of AR genes that have no known activity against the specific antibiotic driver.
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