Gut microbial communities can respond to antibiotic perturbations by rapidly altering their taxonomic and functional composition. However, little is known about the strain-level processes that drive this collective response. Here, we characterize the gut microbiome of a single individual at high temporal and genetic resolution through a period of health, disease, antibiotic treatment, and recovery. We used deep, linked-read metagenomic sequencing to track the longitudinal trajectories of thousands of single nucleotide variants within 36 species, which allowed us to contrast these genetic dynamics with the ecological fluctuations at the species level. We found that antibiotics can drive rapid shifts in the genetic composition of individual species, often involving incomplete genome-wide sweeps of pre-existing variants. These genetic changes were frequently observed in species without obvious changes in species abundance, emphasizing the importance of monitoring diversity below the species level. We also found that many sweeping variants quickly reverted to their baseline levels once antibiotic treatment had concluded, demonstrating that the ecological resilience of the microbiota can sometimes extend all the way down to the genetic level. Our results provide new insights into the population genetic forces that shape individual microbiomes on therapeutically relevant timescales, with potential implications for personalized health and disease.

中文翻译：

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纵向连锁阅读测序揭示抗生素治疗期间人类肠道微生物组的生态和进化反应

肠道微生物群落可以通过快速改变它们的分类和功能组成来响应抗生素的扰动。然而，人们对推动这种集体反应的应变水平过程知之甚少。在这里，我们通过一段时间的健康、疾病、抗生素治疗和恢复，以高时间和遗传分辨率表征单个个体的肠道微生物组。我们使用深度链接读取宏基因组测序来追踪 36 个物种中数千个单核苷酸变异的纵向轨迹，这使我们能够将这些遗传动态与物种水平的生态波动进行对比。我们发现抗生素可以推动单个物种遗传组成的快速变化，通常涉及对预先存在的变异进行不完整的全基因组扫描。这些遗传变化经常在物种丰度没有明显变化的物种中观察到，强调了监测物种水平以下多样性的重要性。我们还发现，一旦抗生素治疗结束，许多广泛的变异会迅速恢复到基线水平，这表明微生物群的生态恢复力有时可以一直延伸到基因水平。我们的研究结果为在治疗相关时间尺度上塑造个体微生物组的种群遗传力提供了新的见解，对个性化健康和疾病具有潜在影响。我们还发现，一旦抗生素治疗结束，许多广泛的变异会迅速恢复到基线水平，这表明微生物群的生态恢复力有时可以一直延伸到基因水平。我们的研究结果为在治疗相关时间尺度上塑造个体微生物组的种群遗传力提供了新的见解，对个性化健康和疾病具有潜在影响。我们还发现，一旦抗生素治疗结束，许多广泛的变异会迅速恢复到基线水平，这表明微生物群的生态恢复力有时可以一直延伸到基因水平。我们的研究结果为在治疗相关时间尺度上塑造个体微生物组的种群遗传力提供了新的见解，对个性化健康和疾病具有潜在影响。