Design, construction, and in vivo augmentation of a complex gut microbiome

Alice G Cheng; Po-Yi Ho; Andrés Aranda-Díaz; Sunit Jain; Feiqiao B Yu; Xiandong Meng; Min Wang; Mikhail Iakiviak; Kazuki Nagashima; Aishan Zhao; Pallavi Murugkar; Advait Patil; Katayoon Atabakhsh; Allison Weakley; Jia Yan; Ariel R Brumbaugh; Steven Higginbottom; Alejandra Dimas; Anthony L Shiver; Adam Deutschbauer; Norma Neff; Justin L Sonnenburg; Kerwyn Casey Huang; Michael A Fischbach

doi:10.1016/j.cell.2022.08.003

Design, construction, and in vivo augmentation of a complex gut microbiome

Cell. 2022 Sep 15;185(19):3617-3636.e19. doi: 10.1016/j.cell.2022.08.003. Epub 2022 Sep 6.

Authors

Alice G Cheng¹, Po-Yi Ho², Andrés Aranda-Díaz², Sunit Jain³, Feiqiao B Yu⁴, Xiandong Meng⁴, Min Wang⁵, Mikhail Iakiviak⁶, Kazuki Nagashima⁶, Aishan Zhao⁶, Pallavi Murugkar⁷, Advait Patil⁶, Katayoon Atabakhsh⁶, Allison Weakley⁴, Jia Yan³, Ariel R Brumbaugh⁶, Steven Higginbottom⁶, Alejandra Dimas⁶, Anthony L Shiver², Adam Deutschbauer⁸, Norma Neff³, Justin L Sonnenburg⁹, Kerwyn Casey Huang¹⁰, Michael A Fischbach¹¹

Affiliations

¹ Department of Gastroenterology & Hepatology, Stanford School of Medicine, Stanford, CA 94305, USA. Electronic address: alicec2@stanford.edu.
² Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
³ Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
⁴ Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.
⁵ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
⁶ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
⁷ ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.
⁸ Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
⁹ Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
¹⁰ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: kchuang@stanford.edu.
¹¹ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: fischbach@fischbachgroup.org.

Abstract

Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex, but not both, limiting their utility. Here, we construct and characterize in vitro a defined community of 104 bacterial species composed of the most common taxa from the human gut microbiota (hCom1). We then used an iterative experimental process to fill open niches: germ-free mice were colonized with hCom1 and then challenged with a human fecal sample. We identified new species that engrafted following fecal challenge and added them to hCom1, yielding hCom2. In gnotobiotic mice, hCom2 exhibited increased stability to fecal challenge and robust colonization resistance against pathogenic Escherichia coli. Mice colonized by either hCom2 or a human fecal community are phenotypically similar, suggesting that this consortium will enable a mechanistic interrogation of species and genes on microbiome-associated phenotypes.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bacteria / genetics
Escherichia coli
Feces
Gastrointestinal Microbiome* / genetics
Germ-Free Life
Humans
Mice
Microbiota*

Abstract

Publication types

MeSH terms

Grants and funding