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The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health
Open accessAbstract
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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“The increase of dysfunctional immunological responses in modern urban societies are posited to be at least in part associated with reduced exposure to commensal and environmental microorganisms that normally prime immunoregulatory circuits and suppress inappropriate inflammation (198).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [198]
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Metadata
- Authors
- Lowry, C. A., Smith, D. G., Siebler, P. H., Schmidt, D., Stamper, C. E., Hassell, J. E., Yamashita, P. S., Fox, J. H., Reber, S. O., Brenner, L. A., Hoisington, A. J., Postolache, T. T., Kinney, K. A., Marciani, D., Hernandez, M., Hemmings, S. M. J., Malan-Muller, S., Wright, K. P., Knight, R., Raison, C. L., & Rook, G. A. W.
- Affiliations
- University of Colorado Boulder (US)
- Universität Ulm (DE)
- VA Rocky Mountain Network (US)
- United States Air Force Academy (US)
- University of Maryland, Baltimore (US)
- The University of Texas at Austin (US)
- Stellenbosch University (ZA)
- University of California San Diego (US)
- University of Wisconsin–Madison (US)
- University College London (GB)
- Corresponding author
- Lowry, Christopher A.
- ORCID
- Venue
- Current Environmental Health Reports
- Published
- 2016-07-19
- Volume
- 3
- Issue
- 3
- Pages
- 270-286
- ISSN
- 2196-5412 (ISSN-L)
- PMC
- PMC5763918
- OpenAlex
- W2476783501
- Cited by
- 172
- References
- 214
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 5 · 2022: 16 · 2021: 16 · 2020: 73 · 2019: 13 · 2018: 15 · 2017: 18 · 2016: 2
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Current Environmental Health Reports (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH086539)
- National Institute on Drug Abuse (R01DA019921)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- hygiene hypothesis, old friends hypothesis, microbiota, immune regulation, mental health, neurodevelopmental disorders, anxiety, mood disorders, inflammation, allergic diseases, asthma, bacterial antigens, helminth antigens, urbanization
- MeSH terms
- Animals, Anxiety, Depression, Humans, Inflammation, Mental Health, Public Health, Immunomodulation, Microbiota
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