during the final weeks of pregnancy, fol- lowed by direct supplementation of the infant. Such studies enroll mothers at high risk for delivering an infant likely to de- velop atopic dermatitis, with the risk factor determined by family history. To date, eight randomized controlled tri- als assessing nine different probiotics or pro- biotic combinations have been published on the primary prevention of eczema, and these trials have produced conflicting results. The large heterogeneity in results might be ex- plained by several factors. First, it is appar- ent that different probiotic strains or com- binations of probiotics would be expected to elicit different effects. This explanation is insufficient, however, based on the observa- tion that studies on the same single strain of Lactobacillus rhamnosus GG (LGG) have reported dramatically different results.4,5 Next, differences in outcomes may be due, in part, to differences in doses or routes of administration. Finally, not all studies have confirmed the colonization of probiotic bacteria in the intestine and some studies have reported alterations in the microflora that were not reflective of the administered bacteria. THE HYGIENE HYPOTHESIS The mechanisms of action by which pro- biotic supplementation might reduce aller- gic diseases have not been elucidated, but could be related to changes in the gut mi- crobiota, immunological effects, or a com- bination of these. Differences in the intesti- nal flora between allergic and non-allergic infants and children have been identified, which predicate the development of aller- gic disease, including eczema, suggesting a potential causal relationship. Specifically, bifidobacteria and lactobacilli are more often found in the microbiota of non-aller- gic children.6,8 The hygiene hypothesis provides a framework for understanding the in- creased incidence of allergic diseases in the context of microbial and immune interac- tions. According to the hygiene hypothesis, the increased prevalence of allergic diseases in children may be associated with reduced exposure to microbial components early in life.9 veloping allergic disease early in life are characterized by a Th2-polarized cytokine profile.10 help to orchestrate the immune response by driving both cell-mediated responses and antibody responses, depending on the activating environment. Naïve Th0 cells can differentiate upon stimulation into ei- ther a Th1 or a Th2 cell lineage, which dif- fer in the cytokines, or chemical signaling molecules, they produce. Different cytokine profiles trigger dif- ferent effects. In general, a Th1-dominant cytokine profile is characterized by inter- feron (IFN)- and is associated with the activation of cellular immunity. In contrast, a Th2 cytokine profile, characterized by IL- - moral immunity, or antibody production. THE PANDA TRIAL (PROBIOTICS AND ALLERGY) Little is known about the strain-specific ef- fects of probiotics on cytokine production in vivo, especially in human infants. How- ever, the PandA trial, the most recent study published on the effectiveness of probiot- ics for the prevention of childhood eczema, included a detailed evaluation of immune modulation in infants.11 This study is The hygiene hypothesis suggests, in part, that a lack of early microbial exposure is associated with an imbalance in the neo- natal development of T helper (Th)1 and (Th)2 cells, contributing to the increased prevalence of Th2-associated allergic dis- eases. Indeed, children at high risk of de- | APRIL 2010 unique in that probiotic strains were se- lected from an original pool of 69 strains in a multi-stage process. Candidate strains were selected based on stability and resis- tance to gastric acid, bile salts, and pancre- atic enzymes,12 and then further selected according to in vitro cytokine production in adult human PBMCs and infant cord blood cells. In the end, Bifidobacterium bifidum As their name suggests, Th cells - tococcus lactis W58, were selected based on their capacity to induce the production of regulatory IL-10 and a reduction in the - tation with combined B. bifidum, B. lactis, and Lc. lactis reduced the incidence of in- fant eczema at three months of age by 58 per cent. Early colonization with Lc. lactis and Bifidobacterium spp. was confirmed by qPCR, and the production of IL-5 and group whether or not those infants devel- oped eczema. An ex vivo analysis, in which whole blood samples obtained from study infants at age three months were stimu- lated in culture, demonstrated a significant reduction in IL-5 and a trend towards de- that the observed reduction in the inci- dence of eczema may have been related to altered immune signaling, specifically a decrease in Th2-mediated immunity. CONCLUSION The PandA trial is the first study of a com- bination probiotic intervention for the pri- mary prevention of childhood eczema in which strains were selected based on in vi- tro cytokine production. This unique com- bination of three probiotic strains reduced the risk of infant eczema by 58 per cent at three months. A beneficial effect persisted through the age of two years, suggesting a lasting impact on immune balance. For article with references, please see www.canadianchiropractor.ca. www.canadianchiropractor.ca
Chiropractic + Naturopathic Doctor April 2010: Page 36
