Modern medicine has proved miraculous in its ability to prevent disease and increase the average life expectancy. However, the decrease in preventable disease has been correlated to an increase in autoimmune disorders. The most probable mechanism for explaining this trend is the hygiene hypothesis. The hygiene hypothesis stipulates that increased standard of living, meaning better hygiene and modern medicine, leads to a decreased exposure to microorganisms which in turn causes autoimmune disorders from diminished natural tolerance. Published online by the Cold Spring Harbor Laboratory Press, a study by Bach and Chatenoud provides evidence to corroborate the hygiene hypothesis via incidence of diabetes in mice living in varied sanitation conditions. The purpose of the experiment was to understand the protective mechanisms underlying infectious disease and thereby deduce a potential therapy for preventing autoimmune disorders.
Insulin dependent diabetes (or type 1 diabetes) is an autoimmune disease where the pancreas does not produce insulin as a result of an immune response directed at the pancreas. Type 1 diabetes is found through out the world, but is most prevalent in northern Europe and Americas. There are progressively less cases as one travels south (Figure 1). The statistical decline in diabetes as one gets closer to the equator is juxtaposed with the increase in infectious diseases (Figure 2). The fact that Figure 1 and Figure 2 are basically mirror images of each other is partly justified by genetics. Genetics explains how isolated populations have increased incidence of diabetes; however, with globalization genetic differences are relatively diminutive in nature. Particularly shown by increased type 1 diabetes rates for first generation migrants from countries of low rates to countries with high rates (Bodansky et al. 1992).
Figure 1. Frequency of Type 1 diabetes worldwide. Incidence of type 1 diabetes in children 0 - 14 yr. The data used in map creation are from www.eatlas.idf.org
Figure 2. Incidence of childhood diarrheal diseases (the data used in map creation are from www.cdc.gov)
The higher the standard of living, the better the medical care and sanitation conditions. When medical care is superior it is less likely for people to get sick or if they do, they are less likely to remain sick. Additionally, developed countries have better sanitation, as in people are cleaner. On the whole, the consequence is a decrease in exposure to microbes at a young age. The study by Bach and Chatenoud looked a non-obese diabetic (NOD) mice and exposure to varied hygiene conditions. Incidence of diabetes in the mice, when other environmental factors were controlled, was highest when sanitation conditions were best. As opposed to when sanitation conditions are worse and the frequency of disease decreased. The effects of increased sanitation could be reverse by raising newborns of Caesarean delivery, in unsanitary conditions. Diabetes was completely prevented in mice raised in a clean environment, which were purposefully exposed to an infectious microorganism.
Natural immune tolerance is an organism’s ability to recognize, and thereby not attack, its own proteins or antigens. In autoimmune diseases, the body’s natural tolerance malfunctions so that an immune response is generated against itself. The results can be debilitating and catastrophic for the ability of the body to function correctly. The basis of the hygiene hypothesis is the protective role played by infectious agent in preventing autoimmune disorders. A study by Calcinaro et al., found that NOD mice exhibited lower frequencies of diabetes by using lactobacillus derived from the gut. Some how the body reacting to bacteria from the gut prevents the body from attacking the pancreas to cause diabetes. Bach hypothesized that those immune responses from infectious agents, which are intensive and involve a variety of pathways “compete for consumption of homeostatic factors” with weaker immune responses, such as those from the body’s own cells (2002). The immune system is primed for action against antigens, which has a greater affinity for infectious disease, but in the absence of disease the body can react to antigens from its own cells. Bystander suppression may also be at play, where immunological activity can down regulate close range immune responses by causing regulator molecule for suppression to elongate their live span (Kimball, 2013). Other mechanisms, such as toll-like receptor agonists, may also play a role in the development of autoimmune disorders.
The hygiene hypothesis is logical, but with little experimental evidence to provide supporting proof. Part of the problem lies in the breadth of variables associated with immune system, autoimmune disorders, and antigens. The immune system is astoundingly complex while autoimmune disorders and antigens are innumerous. Thus, to definitively prove the hygiene hypothesis would be a major undertaking requiring considerable effort, time, and money. However, this does not mean potential applications for treatment of autoimmune diseases are not possible. The most likely therapy revolves around development of chemical extracts to illicit an innocuous immune response at a young age. Yet, FDA regulations would probably prevent administering an extract from an infectious disease to a child for the purpose of producing an immune response in an effort to prevent autoimmune disorders. All in all, the hygiene hypothesis is a very likely explanation for the rise of autoimmune disorder and provides a basis for understanding said autoimmune disorders in hopes of stemming the increase
Bach, Jean-Francois. “The effect of infections on susceptibility to autoimmune and allergic diseases.” New England Journal of Medicine. 2002. 347: 911 – 20.
Bach, Jean-Francois and Lucienne Chatenoud. “The Hygiene Hypothesis: An Explanation for the Increased Frequency of Insulin-Dependent Diabetes.” Cold Spring Harb Perspect Med. Febuary, 2012 doi: 10.1101/cshperspect.a007799
Bodansky, H.J., Staines A., Stephenson C., Haigh D., Cartwright R. "Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population." Br Med J. 1992. 304: 1020–1022.
Calcinaro, F, S. Dionisi, M. Marinaro, P. Candeloro, V. Bonato, S. Marzotti , R. B. Corneli, E. Ferretti, A. Gulino, F. Grasso, C. De Simone, U. Di Mario, A. Falorni, M. Boirivant, F. Dotta. “Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse.” Diabetologia. 2005. 48: 1565–1575.
Kimball, John. "Immunological Tolerance." The Saylor Foundation. March 27 2013. (http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Tolerance.html).