As covered in our first article in this series, there has been a worrying trend towards greater prevalence of autoimmune diseases such as asthma, atopic dermatitis (eczema), and psoriasis. These diseases arise when the body’s immune system is unable to discern invaders from the self and it starts attacking the body’s own cells. In the previous article we presented evidence to autism is an immune system disorder. Therefore, it is important to understand what is causing this dramatic rise in immune system dysfunction/autoimmunity and what we can do about it.
One idea proposed to explain why our immune systems are increasingly dysfunctional is the hygiene hypothesis. The hygiene hypothesis states that too much cleanliness and the lack of exposure to pathogens is impairing the development and function of the immune system. There is a clear inverse correlation when the trends of infectious diseases are compared against the increasing trends of autoimmune diseases. However, correlation does not always equate with causation so we must delve deeper into the cause of the autoimmune and allergic disease to see if this trend can be explained immunologically.
Adapted from JF Bach, The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases - New England Journal of Medicine, 200216
To prove the hygiene hypothesis with human clinical trials would be unethical. However, there are animal studies that have demonstrated animals raised in a sterile environment have more autoimmune diseases than their normal counterparts. In nonobese diabetic (NOD) mice, sterile living environments increased the incidence of diabetes from 40 percent to 80 percent.2
Diabetes is prevented in NOD mice by infecting the young mice with various pathogens such as mycobacteria3, murine hepatitis virus4, lactate dehydrogenase virus5, or schistosoma7 and filariae8 worms. Interestingly, treatment with killed bacteria (complete Freund’s adjuvant)9 or bacterial extracts (streptococci10 or klebsiellae14) offered similar degree of protection against diabetes in NOD mice.
Bacterial Lysate
Similarly, in humans, exposure to antigens and pathogens can elicit benefits as well. A meta study that analyzed data from 19 studies showed that children given bacterial lysate, or broken up and dead bacteria, had 22-24% improvement in allergy and asthma symptoms.1 Immune cells called T-cells can differentiate into Th1 or Th2 subtypes. It is thought that exposing the immune system to bacteria through the gut can help the immune system develop and better differentiate between self and non-self cells. Allergic responses are associated with the Th2 subtypes and in the bacterial lysate treated group, Th1 levels were increased. As expected, not many adverse reactions occurred from treatment with bacterial lysate.
While Th2 cells are associated with allergies such as asthma, atopic dermatitis, and allergic rhinitis, a Th1 cell response is associated with autoimmune diseases (i.e. Diabetes Type 1, rheumatoid arthritis). However, it does not appear to be beneficial to solely shift the T helper cell response to either Th1 or Th2. Helper T cells are regulated by Treg cells. Indeed, the T cell profile in autistic spectrum disorder has increases in both Th1 and Th2 and lower Treg levels, with disease severity correlated with lower Teff/Treg levels6.
Natural Infections and Antibiotic Use
The immune system requires stimulation and exposure to pathogens to develop normally and reduce allergic/autoimmune diseases. Childhood infection with varicella zoster virus, or chicken pox, has been found to lower the risk of developing atopic dermatitis by 45% later in life11. Early respiratory infections acquired before 6 months of age reduced the risk of developing atopic dermatitis later in life by 49%12. Furthermore, repeated antibiotic use in childhood has been associated with a 12% increase in asthma diagnosis later in life after adjusting for confounding variables13. Antibiotic use tends to disrupt the normal gut flora as many are broad-spectrum and do not specifically target pathogens. For this reason, we recommend probiotic use after antibiotic use.
Does this mean that children should be exposed to all pathogens? Not necessarily, as certain infectious agents can trigger allergic or autoimmune diseases. Does it mean that we should be less obsessed about sanitation and cleanliness? Perhaps. There are some things to keep in mind to help develop a healthy immune system.
Vitamin D
Vitamin D is one of the most important vitamins for proper immune function. Autoimmune diseases are correlated with lower vitamin D levels. One recent study in the British Medical Journal found that daily supplementation with Vitamin D for 5 years (with or without omega-3 oil) reduced autoimmune diseases by 22%.
Furthermore, there is a relationship between the risk of autoimmune diseases and the longitude at which a person resides. The further away a person is from the equator, the greater the risk of autoimmune disease. Since the amount of vitamin D a person gets is correlated to the amount of sunlight they receive, it is thought that people closer the poles that receive less sunlight have a higher risk of autoimmune disease.
Adapted from Kurtkzke23, Green and Patterson24
Probiotics
Probiotics are known good bacteria that interact with the immune system. The gut makes up much of the immune system through the gut associated lymphatic tissue (GALT) and is where most of the immune system is exposed to microbial life. It would make sense that the immune system can be modulated through changes in the gut microflora. Several studies have noted that probiotic supplementation can increase the number of Treg cells that inhibit autoimmunity17-19.
Changing timing/amount of vaccinations
Vaccines can be thought of as “target practice” for the immune system. The best vaccines are live attenuated or weakened versions of actual pathogens. These mimic the pathogen well and provide great training for the immune system. These include varicella and measles, mumps, and rubella (MMR) vaccines. Usually, however, vaccines contain dead parts or bits of a pathogen along with an immunostimulatory component such as aluminum adjuvant to provoke the immune system to mount a response to the foreign antigen.
Recent studies that aluminum adjuvant exposure results in a dose-dependent increased risk in asthma20. This means that the more aluminum adjuvant a child received from vaccinations, the greater the risk of developing asthma. Other studies have found that delaying the DTAP vaccine reduced the risk of developing eczema or atopic dermatitis. This was found to be true across two large populations and continents, in Australia21 and Denmark22. The Australian population was found to have a 43% lower chance of developing atopic dermatitis if DTAP vaccination was delayed by a month.
While there is no doubt that vaccines have been beneficial for humanity, not enough research has gone into the long-term effects and ancillary effects of vaccines on the immune system. Some have proposed that “hyper-vaccination” is resulting in immune dysfunction/dysregulation in children. For more information on this topic, we recommend the book “Vaccine Friendly Plan” by Dr. Paul Thomas, M.D. to come up with a reasonable immunization plan for your young child.
In conclusion, there are a number of things you can change about your lifestyle and nutrition to help lower the chances of developing an immune disorder. We recommend the regular consumption of probiotics, vitamin D, and a balanced approach to infectious diseases that weighs the risks and benefits.
Works Cited:
- https://onlinelibrary.wiley.com/doi/full/10.1111/pai.13572
- https://diabetesjournals.org/diabetes/article/40/2/259/8291/Influence-of-Environmental-Viral-Agents-on
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905159/
- https://pubmed.ncbi.nlm.nih.gov/1647335/
- https://pubmed.ncbi.nlm.nih.gov/1489482/
- https://www.sciencedirect.com/science/article/pii/S1750946722001726
- https://pubmed.ncbi.nlm.nih.gov/10320614/
- https://pubmed.ncbi.nlm.nih.gov/11527407/
- https://pubmed.ncbi.nlm.nih.gov/2139617/
- https://pubmed.ncbi.nlm.nih.gov/3956883/
- https://www.sciencedirect.com/science/article/abs/pii/S0091674910009036
- https://academic.oup.com/cid/article/34/5/620/317632
- https://publications.aap.org/pediatrics/article-abstract/123/3/1003/71712/Antibiotic-Use-in-Children-Is-Associated-With
- https://www.pnas.org/doi/10.1073/pnas.88.22.10252
- https://www.bmj.com/content/376/bmj-2021-066452.full
- https://www.nejm.org/doi/full/10.1056/nejmra020100
- https://www.hindawi.com/journals/bmri/2022/6131069/
- https://karger.com/iaa/article-abstract/184/3/291/835353/Multistrain-Probiotics-Supplement-Alleviates
- https://www.sciencedirect.com/science/article/pii/S0147651322009009
- https://www.sciencedirect.com/science/article/pii/S187628592200417X
- https://onlinelibrary.wiley.com/doi/abs/10.1111/all.12830
- https://www.sciencedirect.com/science/article/abs/pii/S2213219820310023
- https://pubmed.ncbi.nlm.nih.gov/10871801/
- https://link.springer.com/article/10.1007/PL00002950