Pandemic of atopic diseases--a lack of microbial exposure in early infancy?

Improved hygienic conditions in Western societies have reduced early microbial exposure, which has been proposed as a reason for the continuously rising prevalence of atopy and subsequent atopic diseases: atopic eczema, allergic rhinitis and asthma (The Hygiene Hypothesis of Allergy). This hypothesis is supported by immunological data showing that the immune response to microbial antigens, both pathogenic and non-pathogenic ones, is accompanied by preferential expression of cytokines that counterbalance the T-helper 2-polarized cytokine production of neonates, the continuity of which might lead to enhanced IgE production, atopy, and atopic disease. Experimental, epidemiological and clinical studies, conducted over the last decade, indicate that non-pathogenic microbes in the gut might be a major factor essential for the maturation of the human immune system to a nonatopic mode. A recent randomised, placebo-controlled trial demonstrated that perinatal administration of probiotics, cultures of potentially beneficial bacteria of the healthy gut microflora, halved the later development of atopic eczema during the first two years of life. Some putative mechanisms of action of gut commensals in host-microbe interactions have been described. Two structural components of bacteria, the lipopolysaccharide portion of Gram-negative bacteria and specified CpG motif in bacterial DNA, activate immunomodulatory genes via Toll-like receptors present e.g. on intestinal epithelial cells thus controlling physiological cytokine milieu in the gut. Probiotics have also been shown to reverse increased intestinal permeability and to reduce antigen load in the gut by degrading and modifying macromolecules. The actual preventive role of natural and genetically constructed supplementary microbes in the development of immunological diseases, like allergy, remains to be elucidated.