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Dysbiosis and the immune system

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.

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.

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Figure 1: A schematic of a conceptual energy landscape harbouring multiple possible stable states of symbiosis and dysbiosis.
Figure 2: Innate and adaptive immunity in the regulation of microbial homeostasis.
Figure 3: The impact of dysbiosis on the host immune system.
Figure 4: The intestinal microbiota and disease development.

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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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Glossary

Xenobiotics

Small chemical compounds that enter an organism unnaturally, such as drugs or pollutants.

Koch's postulates

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.

Alpha diversity

Alpha diversity describes species richness within a site, in contrast to beta diversity, which refers to differences in species composition between sites.

Antimicrobial peptides

Host-derived peptides that are part of the innate immune system and function in host defence against microorganisms.

Metabolic syndrome

A syndrome of co-occurring conditions, including elevated levels of plasma glucose, high blood pressure, abdominal obesity, elevated serum triglyceride levels and low serum high-density lipoprotein levels, that collectively increase the risk of diabetes, stroke and heart disease.

Inflammasomes

Multiprotein complexes composed of a NOD-like receptor protein, the adaptor protein ASC and caspase 1. Inflammasomes contribute to the secretion of interleukin-1β (IL-1β) and IL-18 by activating caspase 1.

Innate lymphoid cells

(ILCs). Cells of the lymphoid lineage that do not express antigen-specific receptors, but orchestrate tissue homeostasis and immunity through cytokine secretion.

Metabolome

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

Probiotics

Microorganisms that are administered to an organism to benefit the host.

Prebiotics

Ingredients of food that promote the growth and metabolism of beneficial microorganisms in the host.

Human microbiome project

A consortium project with the goal of comprehensively describing the commensal microorganisms associated with health and disease in humans.

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Levy, M., Kolodziejczyk, A., Thaiss, C. et al. Dysbiosis and the immune system. Nat Rev Immunol 17, 219–232 (2017). https://doi.org/10.1038/nri.2017.7

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