jueves, 25 de octubre de 2018

The Hygiene Hypothesis and Autoimmune Disorders

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By Yolanda Smith, B.Pharm.Reviewed by Liji Thomas, MD

The hygiene hypothesis is a hypothesis that suggests that the increased incidence of allergic and autoimmune disorders are linked to the tremendous changes in sanitation standards and practices that occurred in industrializing countries throughout the industrial revolution of the 19th and 20th centuries.

Throughout the last century, striking increases in the incidence of autoimmune diseases such as Type 1 diabetes mellitus and multiple sclerosis were evident.

The same holds good for allergic conditions such as atopic dermatitis, allergic rhinitis and asthma.

Although many factors are likely to be involved, including genetics and other triggering mechanisms, the rapidity of the changes appear to indicate the input of other changes, such as those seen in the environment.

This is supported by the finding that emigrants from a country with a low incidence of autoimmune disease to one with a high incidence of such acquire a high incidence of such conditions in the very first generation.

The associated changes in these countries that have witnessed drastic rises in the incidence of such diseases include the widespread use of antibiotics, milk pasteurization, vaccination against common childhood preventable diseases and a supply of almost sterile water.

In particular, the presence of certain microbes is thought to have a salutary effect on the robust functioning of the human immune system.

Throughout the industrial revolution, drastic changes in sanitation standards led to reduced or almost no exposure to these vital bacteria.

As a result, the function of the immune system was compromised, and the incidence of allergic and autoimmune disease began to rise.

Hygiene Hypothesis and “Old Friends” Hypothesis

Strachan first proposed the hygiene hypothesis in 1989, although some observations of the relationship between sanitation and autoimmune disorders had been noted previously.

An earlier observational study of more that 17,000 children in Britain in 1958 found an inverse relationship between allergic diseases such as hay fever, type 1 diabetes and asthma, and the number of older siblings.

Having attended a day care center early in life, within the first 6 months, protected against the development of asthma and atopy in children.

Another study in 1966 found a relationship between sanitation and the prevalence of multiple sclerosis. However, these findings were later extended to asthma and autoimmune diseases.

In 2003, Graham Rook refined the hygiene hypothesis to become the “old friends” hypothesis. This served to overcome some shortcomings of the original one. Notably, the “old friends” hypothesis places an emphasis on the ancient microbes that were present throughout human evolution, rather than childhood infections that reduced in incidence greatly throughout the same time period.

Relationship with Autoimmune Diseases

Diverse mechanisms have been proposed to explain the relationship between microorganisms and the prevention of autoimmune diseases.

The “old friends” microbes and the human immune system, including the distinctive antigens of the microbes, may work together in a reciprocal relationship. These antigens have been suggested to stimulate stronger immune responses, especially as compared to the autoantigens associated with autoimmune disorders.

Competition for cytokines, major histocompatibility complex (MHC) receptors and growth factors that are required for an immune response to occur is likely to be an important mechanism of protection against autoimmune disease.

The weak self-antigens and allergic antigens cannot compete successfully with the strong antigens which elicit immune responses in the case of other infections and parasitoses. Additionally, immunoregulatory interactions with the host toll-like receptors (TLRs) have been proposed as another mechanism.

Type 1 Diabetes

Type 1 diabetes, or insulin-dependent diabetes mellitus (IDDM), is becoming increasingly more prevalent worldwide, in both industrialized and developing countries.

This trend began in the 1970s in industrialized countries and continues today to become a public health problem in some countries, such as Finland. Additionally, younger children are now being seen to be affected by IDDM, including children under the age of 2 years, which was not before noted.

Multiple Sclerosis

In 1966, Leibowitz published an epidemiological study that observed a positive relationship between the prevalence of multiple sclerosis and levels of sanitation. It appeared that high levels of sanitation, such as those in the temperate areas of Israel, were associated with a higher risk of multiple sclerosis when compared to areas of lower sanitation, such as in tropical areas. This relationship has been further supported by other epidemiological studies designed to investigate the impact of the hygiene hypothesis on autoimmune diseases.

Inflammatory Bowel Diseases

The incidence of Crohn’s disease, ulcerative colitis and primary biliary cirrhosis is also increasing. This rise may be due in part to improved medical access and diagnostic techniques, but cannot be linked solely to these explanations. For this reason, an environmental link and the hygiene hypothesis is also thought to be involved.