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Microbiota-mediated colonization resistance: mechanisms and regulation

Nature Reviews Microbiology volume 21, pages 347–360 (2023)Cite this article

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Abstract

A dense and diverse microbial community inhabits the gut and many epithelial surfaces. Referred to as the microbiota, it co-evolved with the host and is beneficial for many host physiological processes. A major function of these symbiotic microorganisms is protection against pathogen colonization and overgrowth of indigenous pathobionts. Dysbiosis of the normal microbial community increases the risk of pathogen infection and overgrowth of harmful pathobionts. The protective mechanisms conferred by the microbiota are complex and include competitive microbial–microbial interactions and induction of host immune responses. Pathogens, in turn, have evolved multiple strategies to subvert colonization resistance conferred by the microbiota. Understanding the mechanisms by which microbial symbionts limit pathogen colonization should guide the development of new therapeutic approaches to prevent or treat disease.

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Fig. 1: Direct mechanisms of colonization resistance.
Fig. 2: Indirect mechanisms of colonization resistance.
Fig. 3: Pathogen evasion of colonization resistance.

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Acknowledgements

The authors thank B. Lo for critical review of the manuscript. The authors apologize to their colleagues whose work was not cited because of space limitations. G.C.-F. is supported by a K99/R00 award from the US National Institutes of Health. Work in the authors’ laboratory is supported by US National Institutes of Health grants (G.N.).

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  1. These authors contributed equally: Gustavo Caballero-Flores, Joseph M. Pickard.

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  1. Department of Pathology and Rogel Cancer Center, The University of Michigan Medical School, Ann Arbor, MI, USA

    Gustavo Caballero-Flores, Joseph M. Pickard & Gabriel Núñez

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Glossary

Bacteriocins

Antimicrobial peptides produced by bacteria to inhibit the growth of similar or closely related bacteria.

Colonization resistance

Mechanisms by which the intestinal microbiota limits the colonization of pathogens and pathobionts.

Cytokine

Small immunoregulatory protein released by cells that mediates cell-to-cell communication in immune responses.

Germ-free (GF) animals

Animals that are born and raised in isolators without exposure to microorganisms.

Pathobionts

Microorganisms that under normal circumstances live as non-harming symbionts, but under certain conditions, usually involving environmental or genetic alterations, induce disease.

Secretion system

Molecular structure assembled by bacteria that enables them to inject effector proteins directly into the host cytoplasm or other microbial cells.

Prebiotics

Compounds in food that promote the growth or activity of beneficial symbionts.

Probiotics

Live microorganisms that upon administration could confer a health benefit on the host.

Secretory IgA

(sIgA). A dimer of IgA molecules bound by a joining peptide (secretory component). sIgA is the predominant immunoglobulin in mucosal surfaces, including the gut.

Symbionts

Organisms of different species living together in a long-term relationship or symbiosis. Many microbial symbionts are mutualistic in that they and the host benefit from each other, whereas commensals receive benefits from the host, but the host is not helped or harmed.

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Caballero-Flores, G., Pickard, J.M. & Núñez, G. Microbiota-mediated colonization resistance: mechanisms and regulation. Nat Rev Microbiol 21, 347–360 (2023). https://doi.org/10.1038/s41579-022-00833-7

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