Despite the documented antibiotic-induced disruption of the gut microbiota, the impact of antibiotic intake on strain-level dynamics, evolution of resistance genes, and factors influencing resistance dissemination potential remains poorly understood. To address this gap we analyzed public metagenomic datasets from 24 antibiotic treated subjects and controls, combined with an in-depth prospective functional study with two subjects investigating the bacterial community dynamics based on cultivation-dependent and independent methods. We observed that short-term antibiotic treatment shifted and diversified the resistome composition, increased the average copy number of antibiotic resistance genes, and altered the dominant strain genotypes in an individual-specific manner. More than 30% of the resistance genes underwent strong differentiation at the single nucleotide level during antibiotic treatment. We found that the increased potential for horizontal gene transfer, due to antibiotic administration, was ∼3-fold stronger in the differentiated resistance genes than the non-differentiated ones. This study highlights how antibiotic treatment has individualized impacts on the resistome and strain level composition, and drives the adaptive evolution of the gut microbiota.

中文翻译：

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抗生素治疗推动人类肠道抵抗力的多样化。

尽管有文献记载抗生素会引起肠道微生物群的破坏，但抗生素摄入对菌株水平动态、耐药基因进化以及影响耐药性传播潜力的因素的影响仍然知之甚少。为了解决这一差距，我们分析了 24 名接受抗生素治疗的受试者和对照组的公共宏基因组数据集，并结合了一项深入的前瞻性功能研究，其中两名受试者基于培养依赖和独立的方法调查细菌群落动态。我们观察到，短期抗生素治疗改变了耐药组的组成并使其多样化，增加了抗生素耐药基因的平均拷贝数，并以个体特异性的方式改变了优势菌株的基因型。超过30%的耐药基因在抗生素治疗期间在单核苷酸水平上发生了强烈分化。我们发现，由于抗生素的施用，水平基因转移的潜力增加，分化的抗性基因比非分化的抗性基因强约3倍。这项研究强调了抗生素治疗如何对耐药组和菌株水平组成产生个体化影响，并推动肠道微生物群的适应性进化。