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Deconstructing the role of iron and heme in the structure of healthy human gut microbial communities

View ORCID ProfileArianna I. Celis, View ORCID ProfileDavid A. Relman, Kerwyn Casey Huang
doi: https://doi.org/10.1101/2022.01.25.477750
Arianna I. Celis
1Department of Bioengineering, Stanford University, Stanford, CA 94305
2Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305
3Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
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  • ORCID record for Arianna I. Celis
David A. Relman
2Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305
3Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
4Infectious Diseases Section, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304
5Chan Zuckerberg Biohub, San Francisco, CA 94158
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  • For correspondence: kchuang@stanford.edu relman@stanford.edu
Kerwyn Casey Huang
1Department of Bioengineering, Stanford University, Stanford, CA 94305
3Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
5Chan Zuckerberg Biohub, San Francisco, CA 94158
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  • For correspondence: kchuang@stanford.edu relman@stanford.edu
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Summary

The response of the human gut microbiome to disruptions is often difficult to discern without model systems that remove the complexity of the host environment. Fluctuations in iron availability provide a case in point: the responses of pathogenic bacteria to iron in vitro are much better understood than those of the indigenous human gut commensal microbiota. In a clinical study of iron supplementation in healthy humans, we identified gradual, participant-specific microbiota shifts correlated with bacterial iron internalization. To identify direct effects due to taxon-specific iron sensitivity, we used stool samples from these participants as inocula to derive in vitro communities. Iron supplementation of these communities caused small shifts in structure, similar to in vivo, whereas iron deprivation dramatically inhibited growth with irreversible and cumulative reduction in diversity and replacement of some dominant species. Sensitivity of individual species to iron deprivation during growth in axenic culture generally predicted iron dependency in a community context. Finally, exogenous heme acted as a source of inorganic iron to prevent depletion of some community members. Our results highlight the complementarity of in vivo and in vitro studies in deconstructing how environmental factors affect gut microbiome structure.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 26, 2022.
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Deconstructing the role of iron and heme in the structure of healthy human gut microbial communities
Arianna I. Celis, David A. Relman, Kerwyn Casey Huang
bioRxiv 2022.01.25.477750; doi: https://doi.org/10.1101/2022.01.25.477750
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Deconstructing the role of iron and heme in the structure of healthy human gut microbial communities
Arianna I. Celis, David A. Relman, Kerwyn Casey Huang
bioRxiv 2022.01.25.477750; doi: https://doi.org/10.1101/2022.01.25.477750

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