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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. Copyright © 2023 Elsevier Inc. All rights reserved.


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. Strain dropouts reveal interactions that govern the metabolic output of the gut microbiome. Cell. 2023 Jun 22;186(13):2839-2852.e21

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PMID: 37352836

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