May 16, 2012

What About Infections and the Hygiene Hypothesis?

In 1989, Strachan  proposed that allergic diseases could be prevented by infections in early childhood, and the transmission of them by unhygienic contact with older siblings. Smaller family size, higher standard of living, and personal cleaning reduced the chances of spreading “protective” infections, originating the hygiene
A recent comparison of two genetically related but cultural and socio-economic different populations (Russian and Finnish) evidenced higher specific IgE levels in Finnish but more total IgE and specific microbial antibodies in Russians.
Enterovirus infection represented the strongest protective factor against allergen
In this direction, farmers’ children from a rural environment were evaluated for atopic symptoms (by questionnaire) and atopy (by skin test), as well as endotoxin measurement. Compared to non-farmers’ children, they presented significantly fewer symptoms of current asthma (adjusted OR 0.67; 95% CI 0.49–0.91; P = 0.01) and rhinitis (OR 0.50; 95% CI 0.33–0.77; P = 0.002). If having unpasteurized milk
also, a significant reduction of atopy (OR 0.24; 95% CI 0.10–0.53; P = 0.001) and current eczema symptoms were added (OR 0.59; 95% CI 0.40–0.87; P = 0.008), while reducing IgE (P < 0.001) and increasing IFNg (P = 0.02). Pasteurized milk, vaccinations, early use of antibiotics, and the westernized lifestyle with less exposure to infectious agents could contribute to this lack of stimulation, essential in the first years of life to change the initial Th2 profile toward a Th1 just not to favor atopy development.
Ten years ago the hygiene hypothesis was suggested, an extensive analysis was done to determine its current relevance, and the conclusions were:
 (a) atopic diseases, but not necessarily asthma, are highly prevalent in smaller and more affluent families;
(b) the postulate of protective infections against atopy is immunologically plausible; the reversal is inconclusive;
(c) the modulating effects of antibiotic therapy and diet influencing intestinal flora need to be evaluated extensively;
(d) The inverse association of family size and allergic sensitization could potentially help to discern underlying causes of the increasing prevalence of atopic diseases.
However, the Th1/Th2 paradigm and how it fits in the hygiene hypothesis must be analyzed. Table 1 considers how all these factors affect both Th2 and Th1 illnesses, and its scheme outlines factors influencing immune system development at different time points.
In this context, genetically inheritance should be the beginning, while the attributable genetic risk ranges from 30% to 80% depending on the disease considered.
Then, susceptibility to multiple exposures will determine if “western and industrialized world” affects the development of atopic diseases in these individuals.
There, developing countries with the objective of reaching a better quality of life increase their risk as shown by the increased atopic prevalence in people who migrated to developed regions and in urban cities when compared to rural.
As a conclusion, we do not need to go back in evolution, we must maintain the control over infections, but need to clarify the role of each microbial stimulus (especially at the gastrointestinal tract), in parallel with genetic background and every co-factor. Large longitudinal birth cohort studies, getting representative
biological and environmental samples, will help us in the future.

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