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The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health

  • Early Life Environmental Health (J Sunyer, Section Editor)
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Abstract

The hygiene or “Old Friends” hypothesis proposes that the epidemic of inflammatory disease in modern urban societies stems at least in part from reduced exposure to microbes that normally prime mammalian immunoregulatory circuits and suppress inappropriate inflammation. Such diseases include but are not limited to allergies and asthma; we and others have proposed that the markedly reduced exposure to these Old Friends in modern urban societies may also increase vulnerability to neurodevelopmental disorders and stress-related psychiatric disorders, such as anxiety and affective disorders, where data are emerging in support of inflammation as a risk factor. Here, we review recent advances in our understanding of the potential for Old Friends, including environmental microbial inputs, to modify risk for inflammatory disease, with a focus on neurodevelopmental and psychiatric conditions. We highlight potential mechanisms, involving bacterially derived metabolites, bacterial antigens, and helminthic antigens, through which these inputs promote immunoregulation. Though findings are encouraging, significant human subjects’ research is required to evaluate the potential impact of Old Friends, including environmental microbial inputs, on biological signatures and clinically meaningful mental health prevention and intervention outcomes.

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Acknowledgments

Effort undertaken during the preparation of this review was sponsored by the Department of the Navy, Office of Naval Research Multidisciplinary University Research Initiative (MURI) Award, Award No. N00014-15-1-2809.

Author information

Authors and Affiliations

  1. Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, 1725 Pleasant Street, Boulder, CO, 80309-0354, USA

    Christopher A. Lowry, David G. Smith, Philip H. Siebler, Dominic Schmidt, Christopher E. Stamper, James E. Hassell Jr., Paula S. Yamashita, James H. Fox & Kenneth P. Wright

  2. Laboratory for Molecular Psychosomatics, Clinic for Psychosomatic Medicine and Psychotherapy, University of Ulm, D-89081, Ulm, Germany

    Stefan O. Reber

  3. Departments of Psychiatry, Physical Medicine & Rehabilitation, University of Colorado, Anschutz School of Medicine, Aurora, CO, 80045, USA

    Lisa A. Brenner

  4. Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC), Veterans Integrated Service Network (VISN) 19, Denver, CO, 80220, USA

    Lisa A. Brenner

  5. Department of Civil and Environmental Engineering, United States Air Force Academy, Colorado Springs, CO, 80840, USA

    Andrew J. Hoisington

  6. University of Maryland School of Medicine, Baltimore, MD, USA

    Teodor T. Postolache

  7. Rocky Mountain MIRECC, Denver, CO, 80220, USA

    Teodor T. Postolache

  8. VISN 5 MIRECC, Baltimore, MD, 21201, USA

    Teodor T. Postolache

  9. Civil, Architectural and Environmental Engineering, University of Texas Austin, Austin, TX, 78712, USA

    Kerry A. Kinney

  10. Qantu Therapeutics, Inc., Lewisville, TX, 75057, USA

    Dante Marciani

  11. Department of Civil, Environmental and Architectural Engineering, University of Colorado Boulder, Boulder, CO, 80309, USA

    Mark Hernandez

  12. Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, 7505, South Africa

    Sian M. J. Hemmings & Stefanie Malan-Muller

  13. Departments of Pediatrics and Computer Science and Engineering, and Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, 92093, USA

    Rob Knight

  14. School of Human Ecology and School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706, USA

    Charles L. Raison

  15. Center for Clinical Microbiology, UCL (University College London), WC1E 6BT, London, UK

    Graham A. W. Rook

Authors
  1. Christopher A. Lowry
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  2. David G. Smith
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  3. Philip H. Siebler
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  4. Dominic Schmidt
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  5. Christopher E. Stamper
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  6. James E. Hassell Jr.
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  7. Paula S. Yamashita
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  8. James H. Fox
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  9. Stefan O. Reber
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  10. Lisa A. Brenner
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  11. Andrew J. Hoisington
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  12. Teodor T. Postolache
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  13. Kerry A. Kinney
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  14. Dante Marciani
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  15. Mark Hernandez
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  16. Sian M. J. Hemmings
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  17. Stefanie Malan-Muller
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  18. Kenneth P. Wright
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  19. Rob Knight
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  20. Charles L. Raison
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  21. Graham A. W. Rook
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Corresponding author

Correspondence to Christopher A. Lowry.

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Conflict of Interest

David G. Smith, Philip H. Siebler, Dominic Schmidt, Christopher E. Stamper, James E. Hassell Jr., Paula S. Yamashita, James H. Fox, Stefan O. Reber, Lisa A. Brenner, Andrew J. Hoisington, Teodor T. Postolache, Kerry A. Kinney, Dante Marciani, Mark Hernandez, Sian M.J. Hemmings, Stefanie Malan-Muller, Rob Knight, Charles L. Raison, and Graham A.W. Rook report that they have no conflict of interest. Christopher A. Lowry serves on the scientific advisory board of Immodulon Therapeutics Ltd. Kenneth P. Wright serves on the scientific advisory board of Torvec Inc., and has research grants from Torvec, Inc. and Philips Inc.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the topical collection on Early Life Environmental Health

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Lowry, C.A., Smith, D.G., Siebler, P.H. et al. The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health. Curr Envir Health Rpt 3, 270–286 (2016). https://doi.org/10.1007/s40572-016-0100-5

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