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.
过往的研究结果证明了抗生素可以引起肠道菌群的失衡和抗药性的增加，但是抗生素如何影响人类肠道菌群和抗药性基因在微观层面的的进化、菌株群体动力学及可能影响抗药性扩散的因素，我们了解甚少。为了回答上述问题，我们把基于宏基因组公共数据的分析及一个深度功能分析的多组学前瞻研究结合在一起进行深度挖掘。我们发现，短期抗生素干预会增加抗药性基因谱在个体之间的差异，提升抗药基因的基因拷贝数及选择个体特异性的的细菌优势菌株。同时，在抗生素干预阶段，30%的的抗药型基因经历了单核苷酸水平的分化。而相比于无显著核苷酸分化的基因，核苷酸分化的基因的水平转移倾向增加了超过三倍。总的来说，本研究结果揭示了抗生素干预会驱动抗药性基因的适应性进化和提升水平基因转移倾向，并对肠道菌群在菌株级别构成和抗药性基因谱具有个体特异性的影响。





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