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

Min Wang; Lucas J Osborn; Sunit Jain; Xiandong Meng; Allison Weakley; Jia Yan; William J Massey; Venkateshwari Varadharajan; Anthony Horak; Rakhee Banerjee; Daniela S Allende; E Ricky Chan; Adeline M Hajjar; Zeneng Wang; Alejandra Dimas; Aishan Zhao; Kazuki Nagashima; Alice G Cheng; Steven Higginbottom; Stanley L Hazen; J Mark Brown; Michael A Fischbach

doi:10.1016/j.cell.2023.05.037

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

Cell. 2023 Jun 22;186(13):2839-2852.e21. doi: 10.1016/j.cell.2023.05.037.

Authors

Min Wang¹, Lucas J Osborn², Sunit Jain³, Xiandong Meng¹, Allison Weakley³, Jia Yan⁴, William J Massey², Venkateshwari Varadharajan², Anthony Horak², Rakhee Banerjee², Daniela S Allende⁵, E Ricky Chan⁶, Adeline M Hajjar², Zeneng Wang², Alejandra Dimas¹, Aishan Zhao¹, Kazuki Nagashima¹, Alice G Cheng¹, Steven Higginbottom⁷, Stanley L Hazen², J Mark Brown², Michael A Fischbach⁸

Affiliations

¹ 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.
² 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.
³ ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
⁴ Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
⁵ Department of Anatomical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA.
⁶ Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
⁷ 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.
⁸ 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.

PMID: 37352836
PMCID: PMC10299816 (available on 2024-06-22)
DOI: 10.1016/j.cell.2023.05.037

Abstract

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.

Keywords: ecology; metabolism; microbiome.

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

Bile Acids and Salts
Clostridiales
Gastrointestinal Microbiome*

Substances

Bile Acids and Salts

Supplementary concepts

Clostridium scindens
Clostridium hylemonae

Abstract

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding