Current Environmental Health Reports

, Volume 3, Issue 3, pp 270–286 | Cite as

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

  • Christopher A. LowryEmail author
  • David G. Smith
  • Philip H. Siebler
  • Dominic Schmidt
  • Christopher E. Stamper
  • James E. HassellJr.
  • 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
  • Kenneth P. Wright
  • Rob Knight
  • Charles L. Raison
  • Graham A. W. Rook
Early Life Environmental Health (J Sunyer, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Early Life Environmental Health


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.


Anxiety Depression Lactobacilli Microbiome Mycobacteria Posttraumatic stress disorder 



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.

Compliance with Ethical Standards

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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Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  • Christopher A. Lowry
    • 1
    Email author
  • David G. Smith
    • 1
  • Philip H. Siebler
    • 1
  • Dominic Schmidt
    • 1
  • Christopher E. Stamper
    • 1
  • James E. HassellJr.
    • 1
  • Paula S. Yamashita
    • 1
  • James H. Fox
    • 1
  • Stefan O. Reber
    • 2
  • Lisa A. Brenner
    • 3
    • 4
  • Andrew J. Hoisington
    • 5
  • Teodor T. Postolache
    • 6
    • 7
    • 8
  • Kerry A. Kinney
    • 9
  • Dante Marciani
    • 10
  • Mark Hernandez
    • 11
  • Sian M. J. Hemmings
    • 12
  • Stefanie Malan-Muller
    • 12
  • Kenneth P. Wright
    • 1
  • Rob Knight
    • 13
  • Charles L. Raison
    • 14
  • Graham A. W. Rook
    • 15
  1. 1.Department of Integrative Physiology and Center for NeuroscienceUniversity of Colorado BoulderBoulderUSA
  2. 2.Laboratory for Molecular Psychosomatics, Clinic for Psychosomatic Medicine and PsychotherapyUniversity of UlmUlmGermany
  3. 3.Departments of Psychiatry, Physical Medicine & RehabilitationUniversity of ColoradoAuroraUSA
  4. 4.Rocky Mountain Mental Illness Research Education and Clinical Center (MIRECC)Veterans Integrated Service Network (VISN) 19DenverUSA
  5. 5.Department of Civil and Environmental EngineeringUnited States Air Force AcademyColorado SpringsUSA
  6. 6.University of Maryland School of MedicineBaltimoreUSA
  7. 7.Rocky Mountain MIRECCDenverUSA
  8. 8.VISN 5 MIRECCBaltimoreUSA
  9. 9.Civil, Architectural and Environmental EngineeringUniversity of Texas AustinAustinUSA
  10. 10.Qantu Therapeutics, Inc.LewisvilleUSA
  11. 11.Department of Civil, Environmental and Architectural EngineeringUniversity of Colorado BoulderBoulderUSA
  12. 12.Department of Psychiatry, Faculty of Medicine and Health SciencesStellenbosch UniversityCape TownSouth Africa
  13. 13.Departments of Pediatrics and Computer Science and Engineering, and Center for Microbiome InnovationUniversity of California San DiegoLa JollaUSA
  14. 14.School of Human Ecology and School of Medicine and Public HealthUniversity of Wisconsin-MadisonMadisonUSA
  15. 15.Center for Clinical MicrobiologyUCL (University College London)LondonUK

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