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High-throughput cultivation of stable, diverse, fecal-derived microbial communities to model the intestinal microbiota

View ORCID ProfileAndrés Aranda-Díaz, View ORCID ProfileKatharine Michelle Ng, Tani Thomsen, Imperio Real-Ramírez, Dylan Dahan, Susannah Dittmar, Carlos Gutierrez Gonzalez, Taylor Chavez, Kimberly S. Vasquez, Taylor H. Nguyen, Feiqiao Brian Yu, Steven K. Higginbottom, Norma F. Neff, Joshua E. Elias, Justin L. Sonnenburg, Kerwyn Casey Huang
doi: https://doi.org/10.1101/2020.07.06.190181
Andrés Aranda-Díaz
1Department of Bioengineering, Stanford University, Stanford, CA 94305
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  • ORCID record for Andrés Aranda-Díaz
Katharine Michelle Ng
1Department of Bioengineering, Stanford University, Stanford, CA 94305
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  • ORCID record for Katharine Michelle Ng
Tani Thomsen
1Department of Bioengineering, Stanford University, Stanford, CA 94305
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Imperio Real-Ramírez
1Department of Bioengineering, Stanford University, Stanford, CA 94305
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Dylan Dahan
2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
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Susannah Dittmar
1Department of Bioengineering, Stanford University, Stanford, CA 94305
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Carlos Gutierrez Gonzalez
3Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305
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Taylor Chavez
1Department of Bioengineering, Stanford University, Stanford, CA 94305
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Kimberly S. Vasquez
2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
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Taylor H. Nguyen
1Department of Bioengineering, Stanford University, Stanford, CA 94305
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Feiqiao Brian Yu
4Chan Zuckerberg Biohub, San Francisco, CA 94158
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Steven K. Higginbottom
2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
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Norma F. Neff
4Chan Zuckerberg Biohub, San Francisco, CA 94158
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Joshua E. Elias
4Chan Zuckerberg Biohub, San Francisco, CA 94158
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Justin L. Sonnenburg
2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
4Chan Zuckerberg Biohub, San Francisco, CA 94158
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Kerwyn Casey Huang
2Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
4Chan Zuckerberg Biohub, San Francisco, CA 94158
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  • For correspondence: kchuang@stanford.edu
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Summary

Mechanistic understanding of the impacts of the gut microbiota on human health has been hampered by limited throughput in animal models. To enable systematic interrogation of gut-relevant microbial communities, here we generated hundreds of in vitro communities cultured from diverse stool samples in various media. Species composition revealed stool-derived communities that are phylogenetically complex, diverse, stable, and highly reproducible. Community membership depended on both medium and initial inoculum, with certain media preserving inoculum compositions. Different inocula yielded different community compositions, indicating their potential for personalized therapeutics. Communities were robust to freezing and large-volume culturing, enabling future translational applications. Defined communities were generated from isolates and reconstituted growth and composition similar to those of communities derived from stool inocula. Finally, in vitro experiments probing the response to ciprofloxacin successfully predicted many changes observed in vivo, including the resilience and sensitivity of each Bacteroides species. Thus, stool-derived in vitro communities constitute a powerful resource for microbiota research.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Lead author: Kerwyn Casey Huang, kchuang{at}stanford.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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High-throughput cultivation of stable, diverse, fecal-derived microbial communities to model the intestinal microbiota
Andrés Aranda-Díaz, Katharine Michelle Ng, Tani Thomsen, Imperio Real-Ramírez, Dylan Dahan, Susannah Dittmar, Carlos Gutierrez Gonzalez, Taylor Chavez, Kimberly S. Vasquez, Taylor H. Nguyen, Feiqiao Brian Yu, Steven K. Higginbottom, Norma F. Neff, Joshua E. Elias, Justin L. Sonnenburg, Kerwyn Casey Huang
bioRxiv 2020.07.06.190181; doi: https://doi.org/10.1101/2020.07.06.190181
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High-throughput cultivation of stable, diverse, fecal-derived microbial communities to model the intestinal microbiota
Andrés Aranda-Díaz, Katharine Michelle Ng, Tani Thomsen, Imperio Real-Ramírez, Dylan Dahan, Susannah Dittmar, Carlos Gutierrez Gonzalez, Taylor Chavez, Kimberly S. Vasquez, Taylor H. Nguyen, Feiqiao Brian Yu, Steven K. Higginbottom, Norma F. Neff, Joshua E. Elias, Justin L. Sonnenburg, Kerwyn Casey Huang
bioRxiv 2020.07.06.190181; doi: https://doi.org/10.1101/2020.07.06.190181

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