Probiotic bacteria for prevention of atopic diseases: design and application

Abstract

Atopic diseases such as (atopic) eczema, food allergy, asthma, and allergic rhinitis are common diseases. The cumulative incidence during childhood is estimated to be 20 to 30%. In countries with a so called ‘’Western lifestyle’’ an increase in the prevalence of atopic diseases has been observed during the last decades. This increase may be due to a reduced exposure to microbial antigens, which is supposed to be a prerequisite for a normal development of the immune system (the hygiene hypothesis). The gastrointestinal tract is the largest surface in direct contact with the outer microbial environment and the intestines harbour the intestinal microbiota with approximately 1014 microbes. Enhanced presence of typical probiotic bacteria in the intestinal microbiota has been associated with reduced prevalence of atopic disease. These differences are already present before the development of atopic diseases, which supports a causal relationship. We aimed to further investigate the possibilities of primary prevention of atopic diseases by perinatal administration of probiotic bacteria and their mechanism of action. In preparation of a clinical trial, probiotic bacteria for primary prevention of atopic diseases in children were selected by their capacity to modulate cytokine responses. The desired immunomodulatory effect of probiotic bacteria would be reduction of Th2 function, and stimulation of Th1 function, tolerance and regulatory immune responses. Specific strains were shown to produce large amounts of IL-10 which coincided with low levels of IL-12p70. Furthermore lactic acid bacteria decreased the production of Th2 cytokines IL-5 and IL-13 which was IL-10 dependent for specific strains since neutralizing IL-10 production resulted in partial to full restoration of Th2 cytokine production and concurred with an increase in IL-12p70 and TNF-α. In addition, the effect of lactic acid bacteria on neonatal immune cells and dendritic cells was investigated and resulted in comparable outcomes. Based on these in vitro studies, B. bifidum, B. lactis, and Lc. Lactis (Ecologic Panda?) were selected. This multi-species probiotics was used in the clinical trial on primary prevention of atopic diseases by probiotic bacteria, the PandA study. In a double-blind, randomized, placebo-controlled trial, probiotic bacteria were administered prenatally to mothers of high-risk children (i.e. positive family history of atopic diseases) and to their offspring during the first 12 months of life. This particular combination of probiotic bacteria was shown to have a preventive effect on the incidence of eczema in high-risk children, which seems to be sustained during the first two years of life. In addition to previous studies, the preventive effect appeared to be established within the first three months of life. Extensive analysis of the intestinal microbiota showed that probiotic supplementation resulted in a significantly different composition of the intestinal microbiota compared to placebo. In addition, probiotic bacteria may only be capable to exert their clinical beneficial effects if they induced a richer and more diverse microbiota, and stimulated or inhibit the presence of specific bacterial species. Furthermore, results from the Panda study suggest that probiotic bacteria modulate the developing immune system but long term effects should be investigated in future studies.