The Hygiene Hypothesis

Medical Author: Charles P. Davis, MD, PhD
Medical Editor: Melissa Conrad Stöppler, MD

The "Hygiene Hypothesis" is a theory that suggests a young child's environment can be "too clean" to effectively stimulate or challenge the child's immune system to respond to various threats during the time a child's immune system is maturing. As a fetus, the immune system is thought to be repressed to avoid rejecting maternal tissue, but at birth, it must start to recognize antigens that may be linked to harmful infections. If the environment is "too clean," the hypothesis suggests that the immune system will not mature properly, and may not react appropriately when the child's immune system encounters germs (viruses, bacteria, fungi, and parasites) or other environmental triggers (pollen, animal dander, fungal spores) later in life. The hypothesis suggests that the lack of immune system challenge results in many people developing immune-related health problems such as asthma.

Although the term "Hygiene Hypothesis" was proposed in the late 1980's, many investigators trace its origins to earlier experiments with animals, mainly mice and rats born and raised in "germ-free" or sterile environments. When experimentally exposed to low doses of an infectious agent that would not harm normally raised rodents, these germ-free adolescent and young adult animals became infected quickly and often died. When examined, the infected animals showed a slow or blunted immune response in these situations. If they were raised to adolescence or adulthood as germ-free animals and then were slowly introduced to bacteria found in their normal gastrointestinal tracts, the rodent's immune response, when exposed to the same pathogen, was much better and the animals usually survived the infection.

The key to understanding how the hygiene hypothesis might explain the high level of asthma in developed nations (and perhaps a number of other diseases such as Crohn's disease, ulcerative colitis, or multiple sclerosis) is knowledge of how the immune system develops, matures, and self-regulates. Although the details of the development and function of the immune system can fill books, a very brief summation is as follows:

1. Stimulation of the immune system causes a number of immune cell types to proliferate (for example, T cells, B cells, macrophages, eosinophils, killer cells), some of which attack infectious agents directly, other produce substances (for example, antibodies and cytokines) that cause or potentiate immune attacks.
2. The hygiene hypothesis suggests that delays in exposure to normal bacteria in the body as well as disease-causing agents make a weaker immune response, and that in turn, produces a weaker ability of the immune system to recognize and respond to suppress the inflammatory response when it is challenged.
3. Researchers suggest that bacterial and parasitic organisms, when exposed to a maturing immune system, cause the continuing development to proceed normally. Consequently, in a "too clean environment," infants and young children may not have their immune systems challenged appropriately, and, according to the hygiene hypothesis, go on to develop problems such as asthma and other immune-related conditions.

Proving the hygiene hypothesis is difficult because of the complexity of the developing immune system, the difficulty in designing ethical studies in infants and young children, and getting control and experimental groups of children who have parents that would allow them to be involved in such studies. Like many hypotheses, aspects or parts of this hypothesis still can be examined with the scientific method. Such work is being done with the hygiene hypothesis. For example, the development of probiotics, the oral introduction of "live microorganisms" to the intestine, is related to this hypothesis. More closely related is the development and study of the use of parasite eggs to modulate the immune response in order to treat inflammatory diseases such as Crohn's disease by modifying the immune response.

Most proponents of the hygiene hypothesis do not suggest that parents expose infants and children to infectious organisms to stimulate their immune response. They do suggest, however, that infants and children may be too protected from other children and the environment so that they fail to develop a normal immune system. This protection or isolation (for example, sterile foods, constant cleaning of the infant and child, social isolation from other children, no outdoor playing) may make children prone to develop immune-related diseases.

Although other investigators suggest increases in asthma and other immune-related diseases are due to other factors (for example, pollution, smoking [secondhand smoke in children], toxin ingestion, and others), each is still a hypothesis until proven by the data gathered and examined by scientific methodology. Unfortunately, this takes time, effort and research money so the clues and eventual answers to the hypothesis will not come easily. Perhaps future data will definitively show that humans can be "too clean."

REFERENCES:

Coronado Biosciences. Products Overview.

Drasar, B and Hill, M. Human intestinal flora. Academic Press, New York, 263p., 1974

Kim, DS et. al. Infection, allergy and the hygiene hypothesis: historical perspective. J Laryngol Otol. 2003 Dec;117(12):946-50.

Scientific American. Can It Be Bad to Be Too Clean?: The Hygiene Hypothesis.

Yazdanbakhsh, M. et. al. Allergy, parasites, and the hygiene hypothesis. Science. 2002 Apr 19;296(5567):490-4.