Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide in the mouse gut depends on the resident microbiota

  1. Daniel Hoces
  2. Giorgia Greter
  3. Markus Arnoldini
  4. Melanie L Stäubli
  5. Claudia Moresi
  6. Anna Sintsova
  7. Sara Berent
  8. Isabel Kolinko
  9. Florence Bansept
  10. Aurore Woller
  11. Janine Häfliger
  12. Eric Martens
  13. Wolf-Dietrich Hardt
  14. Shinichi Sunagawa
  15. Claude Loverdo
  16. Emma Slack  Is a corresponding author
  1. ETH Zurich, Switzerland
  2. Max Planck Institute for Evolutionary Biology, Germany
  3. Weizmann Institute of Science, Israel
  4. University Hospital of Zurich, Switzerland
  5. University of Michigan-Ann Arbor, United States
  6. UPMC, CNRS, France

Abstract

Many microbiota-based therapeutics rely on our ability to introduce a microbe of choice into an already-colonized intestine. In this study, we used genetically barcoded Bacteroides thetaiotaomicron (B. theta) strains to quantify population bottlenecks experienced by a B. theta population during colonization of the mouse gut. As expected, this reveals an inverse relationship between microbiota complexity and the probability that an individual wildtype B. theta clone will colonize the gut. The polysaccharide capsule of B. theta is important for resistance against attacks from other bacteria, phage, and the host immune system, and correspondingly acapsular B. theta loses in competitive colonization against the wildtype strain. Surprisingly, the acapsular strain did not show a colonization defect in mice with a low-complexity microbiota, as we found that acapsular strains have an indistinguishable colonization probability to the wildtype strain on single-strain colonization. This discrepancy could be resolved by tracking in vivo growth dynamics of both strains: acapsular B .theta shows a longer lag-phase in the gut lumen as well as a slightly slower net growth rate. Therefore, as long as there is no niche competitor for the acapsular strain, this has only a small influence on colonization probability. However, the presence of a strong niche competitor (i.e., wildtype B. theta, SPF microbiota) rapidly excludes the acapsular strain during competitive colonization. Correspondingly, the acapsular strain shows a similarly low colonization probability in the context of a co-colonization with the wildtype strain or a complete microbiota. In summary, neutral tagging and detailed analysis of bacterial growth kinetics can therefore quantify the mechanisms of colonization resistance in differently-colonized animals.

Data availability

Relevant numerical source data for Figures and Supplementary is available in Source Data 1. Raw sequencing data accessed on ENA (https://www.ebi.ac.uk/ena/browser/home) under Project ID PRJEB57876 and PRJEB53981. Raw data and code used for generating all figures in this publication are made available in a curated data archive at ETH Zurich (https://www.research-collection.ethz.ch/) under the DOI 10.3929/ethz-b-000557179.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Daniel Hoces

    Department of Health Sciences and Technology, ETH Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Giorgia Greter

    Department of Health Sciences and Technology, ETH Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Markus Arnoldini

    Department of Health Sciences and Technology, ETH Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Melanie L Stäubli

    Department of Biology, ETH Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Claudia Moresi

    Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Anna Sintsova

    Department of Biology, ETH Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Sara Berent

    Department of Health Sciences and Technology, ETH Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  8. Isabel Kolinko

    Department of Health Sciences and Technology, ETH Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  9. Florence Bansept

    Department for Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0562-9222
  10. Aurore Woller

    Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
    Competing interests
    The authors declare that no competing interests exist.
  11. Janine Häfliger

    Klinik für Gastroenterologie und Hepatologie, University Hospital of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  12. Eric Martens

    Department of Microbiology and Immunology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Wolf-Dietrich Hardt

    Department of Biology, ETH Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9892-6420
  14. Shinichi Sunagawa

    Department of Biology, ETH Zurich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3065-0314
  15. Claude Loverdo

    UPMC, CNRS, Paris Cedex 05, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0888-1717
  16. Emma Slack

    Department of Health Sciences and Techn, ETH Zurich, Zurich, Switzerland
    For correspondence
    emma.slack@hest.ethz.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2473-1145

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (NCCR Microbiome)

  • Wolf-Dietrich Hardt
  • Shinichi Sunagawa
  • Emma Slack

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (40B2-0_180953)

  • Emma Slack

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_185128)

  • Emma Slack

Gebert Rüf Stiftung (GR073_17)

  • Claude Loverdo
  • Emma Slack

Botnar Research Centre for Child Health, University of Basel (BRCCH_MIP)

  • Shinichi Sunagawa
  • Emma Slack

Agence Nationale de la Recherche (ANR-21-CE45-0015)

  • Claude Loverdo

Agence Nationale de la Recherche (ANR-20-CE30-0001)

  • Claude Loverdo

Centre National de la Recherche Scientifique (MITI CNRS AAP adaptation du vivant à son environnement)

  • Claude Loverdo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Matthew K Waldor, Brigham and Women's Hospital, United States

Ethics

Animal experimentation: All animal experiments were performed with approval from the Zürich Cantonal Authority under license number ZH120/19.

Version history

  1. Preprint posted: June 19, 2022 (view preprint)
  2. Received: June 20, 2022
  3. Accepted: February 8, 2023
  4. Accepted Manuscript published: February 9, 2023 (version 1)
  5. Version of Record published: March 14, 2023 (version 2)

Copyright

© 2023, Hoces et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Daniel Hoces
  2. Giorgia Greter
  3. Markus Arnoldini
  4. Melanie L Stäubli
  5. Claudia Moresi
  6. Anna Sintsova
  7. Sara Berent
  8. Isabel Kolinko
  9. Florence Bansept
  10. Aurore Woller
  11. Janine Häfliger
  12. Eric Martens
  13. Wolf-Dietrich Hardt
  14. Shinichi Sunagawa
  15. Claude Loverdo
  16. Emma Slack
(2023)
Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide in the mouse gut depends on the resident microbiota
eLife 12:e81212.
https://doi.org/10.7554/eLife.81212

Share this article

https://doi.org/10.7554/eLife.81212

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