Colonization resistance and microbial ecophysiology: using gnotobiotic mouse models and single-cell technology to explore the intestinal jungle

Authors

  • Bärbel Stecher,

    Corresponding author
    1. German Center for Infection Research, Munich, Germany
    • Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, Munich, Germany
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    • These authors contributed equally.
  • David Berry,

    1. Department of Microbial Ecology, Vienna Ecology Center, Faculty of Life Sciences, University of Vienna, Vienna, Austria
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    • These authors contributed equally.
  • Alexander Loy

    1. Department of Microbial Ecology, Vienna Ecology Center, Faculty of Life Sciences, University of Vienna, Vienna, Austria
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Correspondence: Bärbel Stecher, Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University of Munich, Pettenkoferstrasse 9a, Munich 80336, Germany. Tel.: +49 (0)89 2180 729 48; fax: +49 (0)89 2180 728 02; e-mail: Stecher@mvp.uni-muenchen.de

Abstract

The highly diverse intestinal microbiota forms a structured community engaged in constant communication with itself and its host and is characterized by extensive ecological interactions. A key benefit that the microbiota affords its host is its ability to protect against infections in a process termed colonization resistance (CR), which remains insufficiently understood. In this review, we connect basic concepts of CR with new insights from recent years and highlight key technological advances in the field of microbial ecology. We present a selection of statistical and bioinformatics tools used to generate hypotheses about synergistic and antagonistic interactions in microbial ecosystems from metagenomic datasets. We emphasize the importance of experimentally testing these hypotheses and discuss the value of gnotobiotic mouse models for investigating specific aspects related to microbiota–host–pathogen interactions in a well-defined experimental system. We further introduce new developments in the area of single-cell analysis using fluorescence in situ hybridization in combination with metabolic stable isotope labeling technologies for studying the in vivo activities of complex community members. These approaches promise to yield novel insights into the mechanisms of CR and intestinal ecophysiology in general, and give researchers the means to experimentally test hypotheses in vivo at varying levels of biological and ecological complexity.

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