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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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.
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.
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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