Review Article | Published:

Dysbiosis and the immune system

Nature Reviews Immunology volume 17, pages 219232 (2017) | Download Citation

Abstract

Throughout the past century, we have seen the emergence of a large number of multifactorial diseases, including inflammatory, autoimmune, metabolic, neoplastic and neurodegenerative diseases, many of which have been recently associated with intestinal dysbiosis — that is, compositional and functional alterations of the gut microbiome. In linking the pathogenesis of common diseases to dysbiosis, the microbiome field is challenged to decipher the mechanisms involved in the de novo generation and the persistence of dysbiotic microbiome configurations, and to differentiate causal host–microbiome associations from secondary microbial changes that accompany disease course. In this Review, we categorize dysbiosis in conceptual terms and provide an overview of immunological associations; the causes and consequences of bacterial dysbiosis, and their involvement in the molecular aetiology of common diseases; and implications for the rational design of new therapeutic approaches. A molecular- level understanding of the origins of dysbiosis, its endogenous and environmental regulatory processes, and its downstream effects may enable us to develop microbiome-targeting therapies for a multitude of common immune-mediated diseases.

Key points

  • A narrow definition of dysbiosis is as a stable microbial community state that functionally contributes to the aetiology, diagnosis or treatment of a disease.

  • Dysbiosis is often driven by infection and inflammation, diet and xenobiotics, host genetics or the host's environment.

  • Innate and adaptive immunity control the colonization niche of the intestinal microbiota through mechanisms including the production of antimicrobial peptides and IgA antibodies.

  • A dysbiotic microbiota may actively influence its colonization niche by altering the functions of innate and adaptive intestinal immunity.

  • Dysbiosis has been associated with many immune-related human diseases, but in many cases it remains to be established whether dysbiosis is a cause or consequence of the disease.

  • Personalized nutrition and metabolite-based 'postbiotic' therapy may present ways in which to harness the increasing knowledge about dysbiosis in disease for the design of new therapies.

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Acknowledgements

The authors thank the members of the Elinav laboratory for fruitful discussions. They apologize to those authors whose work could not be cited owing to space limitations. A.A.K. is supported by a European Molecular Biology Organization postdoctoral fellowship. C.A.T. received a Boehringer Ingelheim Fonds Ph.D. Fellowship. E.E. is supported by Yael and Rami Ungar, Israel; the Leona M. and Harry B. Helmsley Charitable Trust; the Gurwin Family Fund for Scientific Research; the Crown Endowment Fund for Immunological Research; the estate of Jack Gitlitz; the estate of Lydia Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; the Adelis Foundation; John L. and Vera Schwartz, Pacific Palisades, California, USA; Alan Markovitz, Canada; Cynthia Adelson, Canada; Centre National de la Recherche Scientifique; the estate of Samuel and Alwyn J. Weber; Mr and Mrs Schwarz, Sherman Oaks, California, USA; grants funded by the European Research Council; the German–Israel Binational foundation; the Israel Science Foundation; the Minerva Foundation; the Rising Tide Foundation; and the Alon Foundation scholar award. E.E. is the incumbent of the Rina Gudinski Career Development Chair and a senior fellow of the Canadian Institute For Advanced Research.

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Author notes

    • Maayan Levy
    • , Aleksandra A. Kolodziejczyk
    •  & Christoph A. Thaiss

    These authors contributed equally to this work.

Affiliations

  1. Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.

    • Maayan Levy
    • , Aleksandra A. Kolodziejczyk
    • , Christoph A. Thaiss
    •  & Eran Elinav

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eran Elinav.

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A list of criteria that a microorganism needs to fulfil to be considered the causative agent of a disease, including its presence in all cases of the disease, the ability to grow the microorganism in pure culture, transmissibility of the disease by inoculation of a healthy organism and the re-isolation of the microorganism from the infected host.

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Innate lymphoid cells

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Metabolome

The entirety of small-molecule metabolites at a particular site.

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DOI

https://doi.org/10.1038/nri.2017.7

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