Cleaning UP

The Rise of Allergy and Autoimmune Diseases

  • Trend Overview

    • Historical context indicates a correlation between the rise of autoimmune diseases and decline in infectious diseases.

    • Since the 1950s, diseases such as multiple sclerosis, Crohn’s disease, type 1 diabetes, and asthma have increased by over 300% (1).

    • Concurrent increases in hay fever and food allergies align with a decrease in diseases like mumps, measles, and tuberculosis due to vaccines, antibiotics, and improved hygiene.

Hygiene Hypothesis

  • Origins and Definition

    • The hygiene hypothesis was first proposed in 1989. It suggested that reduced exposure to infections leads to immune system malfunctions.

    • It became popularized as the concept that humans are "too clean for our own good."

  • Criticism of the Hypothesis

    • Many scientists argue against the hygiene hypothesis, emphasizing it oversimplifies the causes of rising allergy rates.

    • Graham Rook (emeritus professor at University College London) states that current understanding indicates non-hygienic factors are more significant.

Emerging Theories

  • New Hypothesis

    • Research suggests early exposure to a diverse range of non-pathogenic microbes is crucial for properly training the immune system.

    • This new perspective implies that reducing hygiene may actually increase infection rates without reversing allergic conditions.

  • Critique of Hygiene Hypothesis

    • Critics argue the label is misleading; it diverts attention from the actual causes of rising autoimmune diseases.

    • Sally Bloomfield (chair of International Scientific Forum on Home Hygiene) states that extreme views against hygiene (e.g., claims not to wash hands) are misguided.

Statistics on Autoimmune and Allergic Disorders

  • Global Comparisons

    • Food allergies in preschool children in Western countries: up to 10%, whereas 2% in mainland China (4).

    • Type 1 diabetes (T1D) rates per 100,000 children: 62.3 in Finland, 6.2 in Mexico, 0.5 in Pakistan (5).

    • Ulcerative colitis (IBD) incidence in Western Europe: 6.5 per 100,000, compared to 3.1 per 100,000 in Eastern Europe (6).

Historical Context of Hygiene Hypothesis

  • Strachan's Observation (1989)

    • David Strachan reported fewer eczema cases in siblings within larger households, leading to the proposal that early infections protect against allergic diseases.

  • Mechanisms Described

    • Proposed link: Bacterial and protozoa infections activate T helper 1 (Th1) cells, which produce cytokines.

    • Reduced infections may diminish Th1 activity, increasing T helper 2 (Th2) activity associated with allergies (7).

Flaws in the Hygiene Hypothesis

  • Helminth Infections

    • Maria Yazdanbakhsh's research shows helminth infections, prevalent in developing countries but rare in developed ones, correlate with lower allergy incidence. Infection leads to high Th2 activity but does not cause allergies.

  • Relevance of Th1 and Th2 Activity

    • Studies indicate autoimmune disorders are linked with increased Th1 activity instead of decreased (8).

  • Reevaluation of Disease Associations

    • Epidemiological studies show that pathogens like measles do not protect against allergies and might increase their risk (10).

New Models in Immunology

  • Old Friends Hypothesis (2003)

    • Proposed by Graham Rook and colleagues, it emphasizes the loss of exposure to benign co-evolved microorganisms as a root cause for immune disorders (11).

    • A suggestion that diverse microbial exposure is vital for immune training rather than solely focusing on infections.

  • Role of the Microbiome

    • Understanding has evolved regarding the human microbiome's importance from birth.

    • Maternal microbes start impacting the baby’s gut before birth and through breastfeeding (12).

  • T Regulatory Cells

    • Regulatory T cells (Treg cells) help in immune response regulation.

    • Exposure to non-pathogenic microbes may activate Treg cells, enhancing immune regulation.

Impacts of Changes in Microbial Exposure

  • Factors Affecting Microbial Exposure

    • Factors contributing to altered immune systems include:

    • Caesarean sections linked to higher allergic disease risk.

    • Pet ownership and farm environments show protection against allergies.

    • Antibiotics associated with increased allergy risks (e.g., asthma, cow’s milk allergy, IBD).

Microbial Diversity Study

  • DIABIMMUNE Study (2008)

    • Conducted in Finland, Estonia, and Russia to analyze gut microbiomes and their impact on T1D and asthma rates.

    • Findings indicate significant differences in gut microbiome and immune responses among populations (13).

Future Directions and Challenges

  • Need for Change in Terminology

    • A conference in 2016 points out the term “hygiene hypothesis” is inadequate and suggested alternatives like “microbiome depletion hypothesis” (15).

  • Public Health Approaches

    • Targeted hygiene is suggested to promote microbial diversity while preventing pathogen spread.

    • Communication of nuanced hygiene messages is essential for reversing trends.

  • Research Gaps

    • Many observational studies exist, but few controlled studies test interventions aimed at immune regulation.

    • Future interventions need timely application within early childhood (before age 3-4) for effectiveness.

  • Focus on Specific Microbial Therapies

    • Developing personalized microbial treatments that condition the immune system without unnecessary dampening is a focus (19).

References

  1. Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347(12):911–920.

  2. Platts-Mills TA (2015) The allergy epidemics: 1870-2010. J Allergy Clin Immunol 136(1):3–13.

  3. Strachan DP (1989) Hay fever, hygiene, and household size. BMJ 299(6710):1259–1260.

  4. Prescott SL, et al. (2013) A global survey of changing patterns of food allergy burden in children. World Allergy Organ J 6(1):21.

  5. International Diabetes Federation (2015) IDF Diabetes Atlas, 7th Ed, www.diabetesatlas.org/across-the-globe.html. Accessed January 20, 2017.

  6. Burisch J, et al.; EpiCom-group (2014) East-West gradient in the incidence of inflammatory bowel disease in Europe: The ECCO-EpiCom inception cohort. Gut 63(4):588–597.

  7. Matricardi PM, Bonini S (2000) High microbial turnover rate preventing atopy: A solution to inconsistencies impinging on the Hygiene hypothesis? Clin Exp Allergy 30(11):1506–1510.

  8. Yazdanbakhsh M, Kremsner PG, van Ree R (2002) Allergy, parasites, and the hygiene hypothesis. Science 296(5567):490–494.

  9. van den Biggelaar AH, et al. (2000) Decreased atopy in children infected with Schistosoma haematobium: A role for parasite-induced interleukin-10. Lancet 356(9243):1723–1727.

  10. Benn CS, et al. (2004) Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life. BMJ 328(7450):1223–1230.

  11. Rook GAW, et al. (2003) Innate immune responses to mycobacteria and the downregulation of atopic responses. Curr Opin Allergy Clin Immunol 3(5):337–342.

  12. Romano-Keeler J, Weitkamp JH (2015) Maternal influences on fetal microbial colonization and immune development. Pediatr Res 77(1-2):189–195.

  13. Vatanen T, et al.; DIABIMMUNE Study Group (2016) Variation in microbiome LPS immunogenicity contributes to autoimmunity in humans. Cell 165(4):842–853.

  14. Katsnelson A (2016) Core Concept: Prebiotics gain prominence but remain poorly defined. Proc Natl Acad Sci USA 113(50):14168–14169.

  15. Bloomfield SF, et al. (2016) Time to abandon the hygiene hypothesis: New perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene. Perspect Public Health 136(4):213–224.

  16. Helmby H (2015) Human helminth therapy to treat inflammatory disorders - where do we stand? BMC Immunol 16:12.

  17. West CE, et al. (2013) Probiotics in primary prevention of allergic disease–follow-up at 8-9 years of age. Allergy 68(8):1015–1020.

  18. Dominguez-Bello MG, et al. (2016) Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med 22(3):250–253.

  19. Chu DM, et al. (2017) Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med 10.1038/nm.4272.