Figure 1: Factors affecting the development of the immune system and subsequent allergic disease


The hygiene hypothesis however, comprises some of the most important factors considered to play a role in this escalation of allergic diseases. This hypothesis states that due to reduced exposure to microbes, viruses and fungi, an imbalance in the immune system develops, leading to the increase in allergic diseases⁵. This hypothesis, originally proposed by Strachan in 1989⁶, observed that hay fever incidence was inversely related to the number of children in the household and eczema in the first year of life was related to the number of older children in the household.

He concluded that over the past century declining family size, improvement in household amenities and higher standards of personal cleanliness have reduced the opportunities for cross-infections in young families. Since then, a number of epidemiological studies have supported these findings.

Factors thought to be of relevance for the prevention of allergic conditions, include:

1. Socio-economic status: Golding et al. found more reported eczema in children growing up in affluent families than non-affluent families⁷.

2. Early childhood infections: Infants experiencing infections early in life may be less likely to develop asthma later in life⁸.

3. Nutrition during infancy and the early years: A diet rich in fermented vegetables, (e.g sauerkraut or pickled vegetables), may lead to lower levels of food and other allergies⁹.

4. Child care arrangements: Day-care attendance before the age of one year, may particularly be beneficial to prevent allergic disease in children from small families, as it may increase their exposure to bacteria and viruses¹⁰.

5. Pet ownership: Keeping cats and dogs is still a very controversial topic in terms of allergy prevention¹¹.

6. Environmental factors: Growing up on a conventional farm where pregnant women and infants, shortly after birth, are in close contact with livestock on a regular basis, may prevent allergic diseases¹². Microbial products are particularly abundant in farming environments where animals such as cattle, pigs, and poultry are kept in the house as is still the practice in some countries.

7. Gut flora: The presence of healthy gut flora i.e. healthy gut bacteria consisting of lactobacillus and bifidobacteria¹³. Furthermore, the use of antibiotics before the age of 2 years, killing off beneficial bacteria, have been linked with an increase in allergic disease¹⁴.
Immune system – the basics

In brief, cells involved in the immune system are divided into:

The cells of the innate system (the most basic part of the immune system) including the skin, mucous membranes of the lungs and gut and the natural microflora (gut bacteria) as well as the phagocytes, macrophages and natural killer cells.

The cells of the adaptive immune system including the lymphocytes such as the T-cells (Th0, Th1, Th2 and Th3) and B-cells^15,16. B-cells are the source of antibodies in the immune system.

Th0 cells are the naive T cells which can develop into either Th1 or Th2 cells.

Th1 cells are important in destroying viruses, bacteria and dead cells.

Th2 cells play an important role in destroying parasites and are involved in allergic reactions.

Th3 cells also called T-regulatory cells, are important in regulating or switching off the immune response.

The cytokines (messengers) produced by these various cells and their interactions with other cells are important in understanding the immunological basis of the hygiene hypothesis.







The immune system and the hygiene hypothesis

The basis of the hygiene hypothesis lies in the fact that there may be a simple imbalance in the Th1 and Th2 cells¹⁷ i.e. Th1 cells are not stimulated due to a lack of exposure to infections and allergens, leading to an over active Th2 system – resulting in allergic disease (Figure 2).

Furthermore, at birth, our immune system is skewed, towards a Th2 immune response, primarily to prevent rejection of the foetus in-utero. This could result in the development of allergic diseases, unless the Th1 response is stimulated by exposure to bacteria and viruses shortly after birth (but a common cold or flu won`t do!). This theory about the Th1/Th2 paradigm and stimulation of the Th1 response is supported by a number of studies¹⁸.

More recently, the role of a mere imbalance of Th1/Th2 cells has been questioned, as disease caused by a Th1 response such as inflammatory bowel disease, diabetes, multiple sclerosis and auto-immune diseases are also escalating. This has led to the hypothesis, that the Th3 (regulatory cells) play the most important role in the hygiene hypothesis (Figure 3) i.e. a lack of exposure to bacteria, viruses and some parasites, leads to an insufficient development of the T-regulatory cells and an insufficient repression/down regulation of both the Th1 and Th2 cells¹⁹.Thus, the increase in allergic disease may be due to increased Th1 response, suppressed regulation by the T-regulatory cells, or a combination of both.

Figure 2: The Th1/Th2 paradigm: Conventional Hygiene Hypothesis

Some scientists question any relevance of the hygiene hypothesis as high asthma prevalence among inner-city children in the USA can not be explained by the hygiene hypothesis.

Living conditions of inner city Afro-Americans and Hispanic-American are characterised by low income, poor hygienic living conditions, high cigarette and drug consumption, multiple allergen triggers and viral infections. However, these populations show highest asthma incidences²⁰ indicating that other factors beside microbial components may also influence the development of allergic diseases, e.g. environment.

Nevertheless, until proven completely irrelevant, epidemiological studies clearly show that the modern infatuation with hygiene and cleanliness in the developed world, along with people living further from nature, is probably a factor in reducing some types of infection but may be contributing to increased allergic reactions.

Clinical relevance

So, what is the message of the hygiene hypothesis? Should we expose our very young infants (or even pregnant women) to disease causing bacteria and viruses which could perhaps be fatal?

Should we stop cleaning our houses or move to conventional farms where children could be exposed to livestock in stables, unpasteurised milk, soil and untreated water? Certainly not, but until we know how much cleaning and what kind of cleaning we should do, researchers have been looking at other practical options to mimic exposure to pathogens.

They have questioned whether it is possible to expose children in a clean and hygienic environment to dirt by feeding them with healthy gut bacteria also known as probiotics. Kalliomaki et al.²¹. conducted a study in Finland by asking mothers with family history of atopy to take either two capsules of placebo or Lactobacillus rhamnosus GG daily (blinded) for two to four weeks before delivery. After delivery, breastfeeding mothers were given the capsules or the children received the agents orally for six months. The children were followed up for four years after birth and it was found that the frequency of atopic eczema in the probiotics group was half that of the placebo group. Thus it was shown that exposure to bacterial products in early life reduces the incidence of atopy.

Another option is to feed children nutritional substances such as prebiotic oligosaccharides that could increase the colonisation of good bacteria in the infant`s gut. Prebiotic oligosaccharides are non-digestible food ingredients that beneficially affect the host (you and me) by selectively stimulating the growth and activity of probiotics in the intestinal tract²².

In other words, prebiotic oligosaccharides are foods not for us, but for our good bacteria because they stimulate their growth in our digestive tracts. Breastmilk is an ideal source of prebiotic oligosaccharides. However, for those mothers who do not breastfeed, a recent study showed a significant reduction in the incidence of eczema, also called atopic dermatitis after supplementation of an infant formula with a specific mixture of prebiotic oligosaccharides²³.

Moro and colleagues²³ completed a blinded study in 206 children where 102 received a formula with prebiotic oligosaccharides and 104 the same formula without prebiotic oligosaccharides. Evaluation of the children at the age of six months showed that ten infants (9.8%) in the intervention group and 24 infants (23.1%) in the control group developed eczema. Other sources of prebiotic oligosaccharides include asparagus, bananas, garlic, barley, chicory, leeks, onion, artichokes and tomatoes.

In summary, as our knowledge about immunity and factors involved in allergy prevention has expanded and related research has emerged, it is becoming apparent that rather than shielding our children from everyday pathogens and dirt, our exposure to the natural world around us actually plays a part in educating our immune system to recognise harmful and harmless substances and thus learns to distinguish between them and develop effective ways to resist.

However, rather than discontinuing cleaning and letting go of personal hygiene, some nutritional factors may provide an answer in safely mimicking exposure to bacteria and viruses. Studies into pre and probiotics so far look promising and are continuing with the aim to provide Healthcare Professionals with more information regarding the use of these products in terms of type, dose and frequency.

Figure 3:

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Giving baby the healthiest possible start leaflet

Research abstracts relating to the immune system







References
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