**8. Five-year view and future expectations**

Involvement of commensal enteric microflora and its components with strong immunoactivating properties in etiopathogenetic mechanism of multifactorial diseases, including atopic diseases has been recently suggested. Regulation of intestinal microflora composition (e.g. by probiotics) offers the possibility to influence the development of mucosal and systemic immunity as well as it can play a role also in prevention and treatment of AD. Progress has been made by the identification of receptors and pathways through which gut microbes influence development of the immune system. Such mechanistic data have moved a field that was once regarded as being on the scientific fringe to the mainstream, and support increased funding to advance this promising area of research in the hope that it might deliver the long awaited answer of how to safely prevent AD.

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efficacious probiotic strains. Further studies should be made for the identification of receptors and pathways through which gut microbes influence development of the

Better understanding of the effects of different probiotic strains and a deeper insight into the mechanisms of the heterogeneous manifestations of AD are needed for the validation of specific strains carrying anti-allergic potential. Therefore, research activities are currently focusing on identification of specific probiotic strains with immunomodulatory potential and on how dietary content interacts with the most efficacious probiotic strains. Moreover, the selection of the most beneficial probiotic strain, the dose, and the timing of supplementation still need to be determined. Further studies should also clarify if any susceptible groups of AD exist and how these groups benefit from supplementation with certain probiotic strains.

Some studies in the management of AD suggest that therapeutic benefit requires a combination of probiotic species (as with VSL#3 or Lacto-mix) or that the component(s) responsible for the anti-inflammatory effect in combination preparations have specific properties that monotherapy probiotics do not [112]. This concept also supports the use of prebiotics that increase concentrations of several commensal immunoregulatory bacteria. Prebiotic use was shown to be associated with a reduction in the faecal concentration of Bacteroides fragilis, but had no effect on Lactobacilli or Bifidobacteria. Genetically modified probiotics will be tested for their ability to attenuate AD thru secreting regulatory cytokines in experimental models as well [113]. In near future, the researchers will look for more appropriate combinations of probiotic species or modified probiotics with/without prebiotic and test them in human/experimental AD models.

Additionally, side effects are very low and they might not be nonexistent, as shown in a set of patients with different diseases. However, probiotics should not be considered as totally harmless, particularly in the immunodeficient host, and more safety studies are needed. As imagined, probiotics may have unpredictable behaviour like all microorganisms, such as unanticipated gene expression in nonnative host environment, or acquired mutations occurring spontaneously via bacterial DNA-transfer mechanisms [114]. And certain probiotics are known to stimulate Th1 immunity, which has been suggested as one of the mechanisms by which they can suppress Th2-mediated allergic diseases [110].
