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Longitudinal linked read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment

View ORCID ProfileMorteza Roodgar, View ORCID ProfileBenjamin H. Good, View ORCID ProfileNandita R. Garud, Stephen Martis, Mohan Avula, Wenyu Zhou, Samuel Lancaster, Hayan Lee, Afshin Babveyh, Sophia Nesamoney, Katherine S. Pollard, View ORCID ProfileMichael P. Snyder
doi: https://doi.org/10.1101/2019.12.21.886093
Morteza Roodgar
1Department of Genetics, Stanford University, Stanford, California, 94305
2Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, 94305
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Benjamin H. Good
3Department of Applied Physics, Stanford University, Stanford, California 94305
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  • For correspondence: bhgood@stanford.edu katherine.pollard@gladstone.ucsf.edu mpsnyder@stanford.edu
Nandita R. Garud
4Department of Ecology and Evolutionary Biology, University of California Los Angeles
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Stephen Martis
5Department of Physics, University of California, Berkeley, CA 94720
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Mohan Avula
1Department of Genetics, Stanford University, Stanford, California, 94305
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Wenyu Zhou
1Department of Genetics, Stanford University, Stanford, California, 94305
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Samuel Lancaster
1Department of Genetics, Stanford University, Stanford, California, 94305
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Hayan Lee
1Department of Genetics, Stanford University, Stanford, California, 94305
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Afshin Babveyh
1Department of Genetics, Stanford University, Stanford, California, 94305
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Sophia Nesamoney
1Department of Genetics, Stanford University, Stanford, California, 94305
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Katherine S. Pollard
6Gladstone Institutes, San Francisco, CA 94158
7Department of Epidemiology & Biostatistics, University of California, San Francisco, Ca 94158
8Chan Zuckerberg Biohub, San Francisco, CA 94158
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  • For correspondence: bhgood@stanford.edu katherine.pollard@gladstone.ucsf.edu mpsnyder@stanford.edu
Michael P. Snyder
1Department of Genetics, Stanford University, Stanford, California, 94305
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  • For correspondence: bhgood@stanford.edu katherine.pollard@gladstone.ucsf.edu mpsnyder@stanford.edu
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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 dynamics 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 find that antibiotics can drive rapid shifts in the genetic composition of individual species, often involving incomplete genome-wide sweeps of pre-existing variants. Interestingly, genetic changes frequently occur in species without obvious changes in relative species abundance, emphasizing the importance of monitoring diversity below the species 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.

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Posted December 23, 2019.
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Longitudinal linked read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment
Morteza Roodgar, Benjamin H. Good, Nandita R. Garud, Stephen Martis, Mohan Avula, Wenyu Zhou, Samuel Lancaster, Hayan Lee, Afshin Babveyh, Sophia Nesamoney, Katherine S. Pollard, Michael P. Snyder
bioRxiv 2019.12.21.886093; doi: https://doi.org/10.1101/2019.12.21.886093
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Longitudinal linked read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment
Morteza Roodgar, Benjamin H. Good, Nandita R. Garud, Stephen Martis, Mohan Avula, Wenyu Zhou, Samuel Lancaster, Hayan Lee, Afshin Babveyh, Sophia Nesamoney, Katherine S. Pollard, Michael P. Snyder
bioRxiv 2019.12.21.886093; doi: https://doi.org/10.1101/2019.12.21.886093

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