Preventive and curative effects of probiotics in atopic patients

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Summary

Normally, the transport of allergens through the intestinal epithelia to the blood is limited. It is hypothesised that if these compounds arrive in the blood circulation, they must percolate through the epithelial cell layer. Thus, food allergy (and thus atopic eczema) implies an increased intercellular leakage of the gut wall. Such increased intercellular leakage is thought to be caused by a slightly changed cellular morphology due to a slight cytopathologic effect because of both a limited decay of the cytoskeleton and a slightly reduced turgor. These events may be due to a reduced production of intracellular metabolic energy in the epithelial cells due to an increased concentration of familiar, frequently occurring, potentially toxic bacterial metabolites, i.e., d-lactic acid and/or ethanol.

In this hypothesis we suggest that adequate probiotics can (i) prevent the increased characteristic intestinal permeability of children with atopic eczema and food allergy, (ii) can thus prevent the uptake of allergens, and (iii) finally can prevent the expression of the atopic constitution. The use of adequate probiotic lactobacilli, i.e., homolactic and/or facultatively heterolactic l-lactic acid-producing lactobacilli, reduces the intestinal amounts of the bacterial, toxic metabolites, d-lactic acid and ethanol by fermentative production of merely the non-toxic l-lactic acid from glucose. Thus, it is thought that beneficial probiotic micro-organisms promote gut barrier function and both undo and prevent unfavourable intestinal micro-ecological alterations in allergic individuals.

Introduction

Recently Kalliomäki et al. [1] reported on the effect of the probiotic Lactobacillus (casei subsp rhamnosus) GG in the primary prevention of atopic disease. In a prospective study they gave daily Lactobacillus GG to mothers for 2–4 weeks before expected delivery, and postnatally for six months to infants at high risk of this disease. From the results they concluded that with this protocol the specific microbe can reduce by half the frequency of atopic eczema, which is regarded as the most relevant expression of atopic constitution during childhood. This new insight might provide an opportunity to devise strategies against allergy [1].

The protocol as used by Kalliomäki et al. [1], seems to guarantee less development of eczema in childhood. However, in this protocol the following two aspects have been combined: (i) before delivery the infant was subjected for 2–4 weeks to an indirect effect of the probiotic via the mother, and (ii) after delivery during six months to the direct effect. The combination makes the real effect of the probiotic in the prevention of eczema difficult to establish. With our microbiological and biochemical experience in the field of intestinal micro-flora [2], [3], [4], we think we can pinpoint and explain the real probiotic effect [5], and thus contribute to new strategies against allergy [6].

Section snippets

Development of intestinal flora in neonates

At every moment the intestinal flora contains several hundreds of bacterial species. The composition of this flora is dynamic because of the continuous presence of many transient bacteria. The core of this flora consists of large numbers of bacteria with a stable metabolic activity. This core mainly defines the many specific properties of the unaffected intestine. Confrontation between microbes and gastrointestinal tract begins instantly after birth. Just before the delivery the human

Intestinal leakage

The transport of allergens through the cells of intestinal epithelia to the blood is limited. If these compounds do still arrive in the blood circulation, then they must percolate through the epithelial cell layer. Thus, food allergy implies an increased intercellular leakage of the gut wall, that is thought to be caused by a slightly changed, i.e., less rigid, cellular morphology due to a minor cytopathologic effect.

Mechanism of intercellular leakage

Cellular morphology is mainly determined by the cellular cytoskeleton, i.e.,

Probiotic reduction of leakage in new-borns

Immediately after delivery the mentioned detoxification systems for ethanol and d-lactic acid in the gut wall and the liver are not sufficiently matured, and thus the intestinal epithelia are extremely sensitive to these metabolites. With increasing maturation of the detoxification systems the chance of leakage and thus of atopic eczema decreases daily. This chance may additionally be reduced by breast feeding and by feeding suitable probiotics to the baby. By nature, breast feeding is thought

Conclusion

This hypothesis suggests a model that supports the conclusion of Kalliomäki et al. [1] that adequate probiotics may reverse the increased characteristic intestinal permeability of children with atopic eczema and food allergy. Adequate numbers of beneficial probiotic micro-organisms promote gut barrier function and both undo and prevent intestinal, micro-ecological alterations in allergic individuals, and finally may reduce or even prevent the expression of the atopic constitution.

Acknowledgement

For the English text corrections we thank Dr. Eric Robertson, Department of Anaesthesia.

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