Longitudinal linked-read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment
- Morteza Roodgar1,2,9,
- Benjamin H. Good3,9,
- Nandita R. Garud4,
- Stephen Martis5,
- Mohan Avula1,
- Wenyu Zhou1,
- Samuel M. Lancaster1,
- Hayan Lee1,
- Afshin Babveyh1,
- Sophia Nesamoney1,
- Katherine S. Pollard6,7,8 and
- Michael P. Snyder1
- 1Department of Genetics, Stanford University, Stanford, California 94305, USA;
- 2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA;
- 3Department of Applied Physics, Stanford University, Stanford, California 94305, USA;
- 4Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, California 90095, USA;
- 5Department of Physics, University of California, Berkeley, California 94720, USA;
- 6Gladstone Institutes, San Francisco, California 94158, USA;
- 7Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94158, USA;
- 8Chan Zuckerberg Biohub, San Francisco, California 94158, USA
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↵9 These authors contributed equally to this work.
Abstract
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.265058.120.
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Freely available online through the Genome Research Open Access option.
- Received April 24, 2020.
- Accepted June 25, 2021.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
