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Microbiota succession throughout life from the cradle to the grave

Nature Reviews Microbiology volume 20, pages 707–720 (2022)Cite this article

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Abstract

Associations between age and the human microbiota are robust and reproducible. The microbial composition at several body sites can predict human chronological age relatively accurately. Although it is largely unknown why specific microorganisms are more abundant at certain ages, human microbiota research has elucidated a series of microbial community transformations that occur between birth and death. In this Review, we explore microbial succession in the healthy human microbiota from the cradle to the grave. We discuss the stages from primary succession at birth, to disruptions by disease or antibiotic use, to microbial expansion at death. We address how these successions differ by body site and by domain (bacteria, fungi or viruses). We also review experimental tools that microbiota researchers use to conduct this work. Finally, we discuss future directions for studying the microbiota’s relationship with age, including designing consistent, well-powered, longitudinal studies, performing robust statistical analyses and improving characterization of non-bacterial microorganisms.

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Fig. 1: The succession of the human microbiota from conception to death.
Fig. 2: Measurements of bacterial diversity across age.
Fig. 3: Primary succession in utero and during early life.
Fig. 4: Secondary succession in adolescence and adult life.
Fig. 5: Late succession approaching the end of life.
Fig. 6: The microbiota after death.

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Acknowledgements

This work was supported by the US National Institute of Justice under award number 2016-DN-BX-0194 (to R.K and J.L.M.) and the US National Institutes of Health under award number U19AG063744 Project 1: Changes in Gut Microbiome (to R.K.). A.H.D. is supported by the Stein Institute for Research on Aging, the Natasha Josefowitz Predoctoral Fellowship and the Reiter Endowed Fellowship.

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  1. These authors contributed equally: Cameron Martino, Amanda Hazel Dilmore.

Authors and Affiliations

  1. Department of Paediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA

    Cameron Martino, Amanda Hazel Dilmore & Rob Knight

  2. Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA

    Cameron Martino

  3. Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA, USA

    Cameron Martino, Dilip Jeste & Rob Knight

  4. Biomedical Sciences Program, University of California, San Diego, La Jolla, CA, USA

    Amanda Hazel Dilmore

  5. Department of Animal Sciences, Colorado State University, Fort Collins, CO, USA

    Zachary M. Burcham & Jessica L. Metcalf

  6. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA

    Dilip Jeste

  7. Department of Neurosciences, University of California San Diego, La Jolla, CA, USA

    Dilip Jeste

  8. Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA

    Dilip Jeste

  9. Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA, USA

    Rob Knight

  10. Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA

    Rob Knight

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Glossary

Keystone community members

Microbial species that have an exceedingly large impact on the stability, or recovery after perturbation, of the whole ecosystem.

Alpha diversity

A measure of within-sample diversity.

Beta diversity

A measure of similarity between samples.

Secondary bile acids

Bile acids that have been altered by the microbiota.

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Martino, C., Dilmore, A.H., Burcham, Z.M. et al. Microbiota succession throughout life from the cradle to the grave. Nat Rev Microbiol 20, 707–720 (2022). https://doi.org/10.1038/s41579-022-00768-z

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