Strain dropouts reveal interactions that govern the metabolic output of the gut microbiome.


Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
22 06 2023
Historique:
received: 11 07 2022
revised: 10 04 2023
accepted: 26 05 2023
pmc-release: 22 06 2024
medline: 26 6 2023
pubmed: 24 6 2023
entrez: 23 6 2023
Statut: ppublish

Résumé

The gut microbiome is complex, raising questions about the role of individual strains in the community. Here, we address this question by constructing variants of a complex defined community in which we eliminate strains that occupy the bile acid 7α-dehydroxylation niche. Omitting Clostridium scindens (Cs) and Clostridium hylemonae (Ch) eliminates secondary bile acid production and reshapes the community in a highly specific manner: eight strains change in relative abundance by >100-fold. In single-strain dropout communities, Cs and Ch reach the same relative abundance and dehydroxylate bile acids to a similar extent. However, Clostridium sporogenes increases >1,000-fold in the ΔCs but not ΔCh dropout, reshaping the pool of microbiome-derived phenylalanine metabolites. Thus, strains that are functionally redundant within a niche can have widely varying impacts outside the niche, and a strain swap can ripple through the community in an unpredictable manner, resulting in a large impact on an unrelated community-level phenotype.

Identifiants

pubmed: 37352836
pii: S0092-8674(23)00589-5
doi: 10.1016/j.cell.2023.05.037
pmc: PMC10299816
mid: NIHMS1905469
pii:
doi:

Substances chimiques

Bile Acids and Salts 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2839-2852.e21

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK101674
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL147823
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK130227
Pays : United States
Organisme : NIDDK NIH HHS
ID : DP1 DK113598
Pays : United States
Organisme : NIAAA NIH HHS
ID : P50 AA024333
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests Stanford University and the Chan Zuckerberg Biohub have patents pending for microbiome technologies on which the authors are co-inventors. M.A.F. is a co-founder and director of Federation Bio and Kelonia, a co-founder of Revolution Medicines, an Innovation Partner at the Column Group, and a member of the scientific advisory board of NGM Bio.

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Auteurs

Min Wang (M)

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; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.

Lucas J Osborn (LJ)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Sunit Jain (S)

ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.

Xiandong Meng (X)

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; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.

Allison Weakley (A)

ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.

Jia Yan (J)

Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.

William J Massey (WJ)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Venkateshwari Varadharajan (V)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Anthony Horak (A)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Rakhee Banerjee (R)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Daniela S Allende (DS)

Department of Anatomical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.

E Ricky Chan (ER)

Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA.

Adeline M Hajjar (AM)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Zeneng Wang (Z)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Alejandra Dimas (A)

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; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.

Aishan Zhao (A)

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; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.

Kazuki Nagashima (K)

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; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.

Alice G Cheng (AG)

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; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.

Steven Higginbottom (S)

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.

Stanley L Hazen (SL)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

J Mark Brown (JM)

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH 44195, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Michael A Fischbach (MA)

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; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: fischbach@fischbachgroup.org.

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