Review series on helminths, immune modulation and the hygiene hypothesis: The broader implications of the hygiene hypothesis
Open accessAbstract
Summary: Man has moved rapidly from the hunter–gatherer environment to the living conditions of the rich industrialized countries. The hygiene hypothesis suggests that the resulting changed and reduced pattern of exposure to microorganisms has led to disordered regulation of the immune system, and hence to increases in certain inflammatory disorders. The concept began with the allergic disorders, but there are now good reasons for extending it to autoimmunity, inflammatory bowel disease, neuroinflammatory disorders, atherosclerosis, depression associated with raised inflammatory cytokines, and some cancers. This review discusses these possibilities in the context of Darwinian medicine, which uses knowledge of evolution to cast light on human diseases. The Darwinian approach enables one to correctly identify some of the organisms that are important for the ‘Hygiene’ or ‘Old Friends’ hypothesis, and to point to the potential exploitation of these organisms or their components in novel types of prophylaxis with applications in several branches of medicine.
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Urbanization and limited natural exposure have been associated with increased chronic disease risk.
“Activities such as hiking promote microbial diversity, which is essential for immune resilience, whereas urbanization and limited natural exposure have been associated with increased chronic disease risk [41,42,43,44,45,46,47].”
Activities such as hiking promote microbial diversity, which is essential for immune resilience.
“Activities such as hiking promote microbial diversity, which is essential for immune resilience, whereas urbanization and limited natural exposure have been associated with increased chronic disease risk [41,42,43,44,45,46,47].”
Cites
Hay fever, hygiene, and household size.
Strachan, D. P. (1989) · BMJ · doi:10.1136/bmj.299.6710.1259 · Cited by 5,054 · see citing works
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009 · see citing works
Convergent adaptation of human lactase persistence in Africa and Europe
Tishkoff, S. A., Reed, F. A., Ranciaro, A., Voight, B. F., Babbitt, C. C., Silverman, J. S., Powell, K., Mortensen, H. M., Hirbo, J. B., Osman, M., et al. (2007) · Nature Genetics · doi:10.1038/ng1946 · Cited by 1,615 · see citing works
Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey
Riedler, J., Braun-Fahrländer, C., Eder, W., Schreuer, M., Waser, M., Maisch, S., Carr, D., Schierl, R., Nowak, D., & von Mutius, E. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06252-3 · Cited by 1,520 · see citing works
The metabolic syndrome, inflammation, and risk of cognitive decline
Yaffe, K. (2004) · JAMA · doi:10.1001/jama.292.18.2237 · Cited by 1,025 · see citing works
Recent acceleration of human adaptive evolution
Hawks, J., Wang, E. T., Cochran, G. M., Harpending, H. C., & Moyzis, R. K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707650104 · Cited by 471 · see citing works
Th1, Th2, and Th3 cytokine alterations in major depression
MYINT, A., LEONARD, B., STEINBUSCH, H., & KIM, Y. (2005) · Journal of Affective Disorders · doi:10.1016/j.jad.2005.07.008 · Cited by 371 · see citing works
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Manichanh, C., Borruel, N., Casellas, F., & Guarner, F. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.152 · Cited by 1,160 · see citing works
The biodiversity hypothesis and allergic disease: world allergy organization position statement
Haahtela, T., Holgate, S., Pawankar, R., Akdis, C. A., Benjaponpitak, S., Caraballo, L., Demain, J., Portnoy, J., & von Hertzen, L. (2013) · World Allergy Organization Journal · doi:10.1186/1939-4551-6-3 · Cited by 426 · see citing works
von Hertzen, L., Hanski, I., & Haahtela, T. (2011) · The EMBO Reports · doi:10.1038/embor.2011.195 · Cited by 304 · see citing works
Probiotic Microbes Sustain Youthful Serum Testosterone Levels and Testicular Size in Aging Mice
Poutahidis, T., Springer, A., Levkovich, T., Qi, P., Varian, B. J., Lakritz, J. R., Ibrahim, Y. M., Chatzigiagkos, A., Alm, E. J., & Erdman, S. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0084877 · Cited by 177 · see citing works
Raison, C. L., Lowry, C. A., & Rook, G. A. W. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.161 · Cited by 169 · see citing works
Self-citationMicrobial Reprogramming Inhibits Western Diet-Associated Obesity
Poutahidis, T., Kleinewietfeld, M., Smillie, C., Levkovich, T., Perrotta, A., Bhela, S., Varian, B. J., Ibrahim, Y. M., Lakritz, J. R., Kearney, S. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068596 · Cited by 164 · see citing works
McDade, T. W., Rutherford, J., Adair, L., & Kuzawa, C. W. (2010) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2009.1795 · Cited by 162 · see citing works
Microbiota, immunoregulatory old friends and psychiatric disorders
Rook, G. A. W., Raison, C. L., & Lowry, C. A. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_15 · Cited by 117 · see citing works
Self-citationMcdade, T. W., Tallman, P. S., Madimenos, F. C., Liebert, M. A., Cepon, T. J., Sugiyama, L. S., & Snodgrass, J. J. (2012) · American Journal of Human Biology · doi:10.1002/ajhb.22296 · Cited by 113 · see citing works
Liu, R. T. (2015) · Journal of Abnormal Psychology · doi:10.1037/abn0000043 · Cited by 113 · see citing works
Williamson, L. L., McKenney, E. A., Holzknecht, Z. E., Belliveau, C., Rawls, J. F., Poulton, S., Parker, W., & Bilbo, S. D. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.07.006 · Cited by 84 · see citing works
McDade, T. W., Hoke, M., Borja, J. B., Adair, L. S., & Kuzawa, C. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.08.010 · Cited by 83 · see citing works
Prescott, S. L., Wegienka, G., Logan, A. C., & Katz, D. L. (2018) · BioPsychoSocial Medicine · doi:10.1186/s13030-018-0126-z · Cited by 53 · see citing works
The environmental microbiome, allergic disease, and asthma
Kelly, M. S., Bunyavanich, S., Phipatanakul, W., & Lai, P. S. (2022) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2022.06.006 · Cited by 47 · see citing works
Evolutionary determinants of polycystic ovary syndrome: part 2
Fessler, D. M. T., Natterson-Horowitz, B., & Azziz, R. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.05.016 · Cited by 44 · see citing works
Aliberti, S. M., & Capunzo, M. (2025) · Nutrients · doi:10.3390/nu17040722 · Cited by 29 · see citing works
Mcdade, T. W., Adair, L., Feranil, A. B., & Kuzawa, C. (2011) · American Journal of Human Biology · doi:10.1002/ajhb.21128 · Cited by 22 · see citing works
- Authors
- Rook, G. A. W.
- Affiliations
- The Royal Free Hospital (GB)
- Corresponding author
- Rook, Graham A. W.
- ORCID
- Rook, Graham A. W.
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 2008-12-08
- Volume
- 126
- Issue
- 1
- Pages
- 3-11
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- PMC
- PMC2632706
- OpenAlex
- W2105150055
- Cited by
- 295
- References
- 7
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 10 · 2023: 12 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 18 · 2018: 20 · 2017: 14 · 2016: 18 · 2015: 23 · 2014: 32 · 2013: 23 · 2012: 25
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- hygiene hypothesis, immunomodulation, helminths, old friends hypothesis, microbial exposure, immune dysregulation, allergic diseases, autoimmunity, inflammatory bowel disease, neuroinflammation, atherosclerosis, depression, cancer, evolutionary medicine, disease evolution, prophylaxis
- MeSH terms
- Biological Evolution, Helminthiasis, Host-Parasite Interactions, Humans, Hygiene, Hypersensitivity, Immune System, Inflammation, Models, Immunological
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