Perspective | Published:

Sieving through gut models of colonization resistance

Abstract

The development of innovative high-throughput genomics and metabolomics technologies has considerably expanded our understanding of the commensal microorganisms residing within the human body, collectively termed the microbiota. In recent years, the microbiota has been reported to have important roles in multiple aspects of human health, pathology and host–pathogen interactions. One function of commensals that has attracted particular interest is their role in protection against pathogens and pathobionts, a concept known as colonization resistance. However, pathogens are also able to sense and exploit the microbiota during infection. Therefore, obtaining a holistic understanding of colonization resistance mechanisms is essential for the development of microbiome-based and microbiome-targeting therapies for humans and animals. Achieving this is dependent on utilizing physiologically relevant animal models. In this Perspective, we discuss the colonization resistance functions of the gut microbiota and sieve through the advantages and limitations of murine models commonly used to study such mechanisms within the context of enteric bacterial infection.

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Acknowledgements

E.E. is supported by Y. and R. Ungar; the Leona M. and Harry B. Helmsley Charitable Trust; and grants funded by the European Research Council, and is a senior fellow at the Canadian Institute for Advanced Research (CIFAR) and an International Scholar at the Bill and Melinda Gates Foundation and Howard Hughes Medical Institute (HHMI). This work was supported by grant MR/N00695X/1 from the AMR cross research council initiative under theme 1: Understanding resistant bacteria in the context of the host (C.M.S. and G.F.) and a Royal Society International Collaboration Award for Research Professors, ref: IC160080 (G.F.).

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The authors declare no competing financial interests.

Correspondence to Gad Frankel.

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Fig. 1: Colonization resistance in humans and mouse models.