**3. The intestinal microbiota of allergic ones**

The role of maternal microbiota in the process of preventing allergy has been proven. Infants from allergic parents are at least twice more likely to the risk of developing allergic diseases than nonallergic parents. Microbiota diversity exists between allergic and nonallergic persons. Reduction in the fecal diversity of the bacteroidetes in pregnancy is connected with the prevalence of atopic eczema in their young children [49]. The microbiota of healthy infants with nonallergic parents frequently consists of healthy lactobacilli, representing the role of maternal microbiota in preventing allergic disorders. A decrease in the number of lactobacilli and bifidobacteria and an increase in the colonization of *Staphylococcus aureus* and *Clostridium difficile* are associated with the development of allergic disorders later in life, which shows the abnormality even before the onset of the allergy [50, 51]. Apart from quantitative alterations, qualitative alterations are important in the microbiota. For example, the microbiota of infants suffering from atopic dermatitis (AD) consists of mostly *B. adolescentis* which is mainly forming adult microbiota, whereas *B. bifidum* is the fundamental former of the healthy breastfeeding infants [52, 53]. Bifidobacteria of atopic dermatitis infants encourage the secretion of proinflammatory cytokines, whereas the bifidobacterium of healthy ones encourages the secretion of anti-inflammatory cytokines [54]. Besides, these bifidobacteria have different adhesion behaviors to Caco-2 tissue culture cells [55] and intestinal mucus [56], which seems to be the reason for the reduction in stimulating the immune system. And at last, the metabolic activity of the microbiota composition is different too. Higher levels of butyrate, isovalerate, and caproate in the fecal matter of children with high risk for developing allergy in comparison with normal children are the confirmation of this claim [57].

### **4. Stabilizing intestinal bacterial flora**

The intestine, the largest immune organ of the body, which is the source of the most antibody-producing cells [58] is the target of triggering maturation of the immune system or the restoration of the impaired commensal bacteria. Stimulation of the immune system is one of the most impressive functions of the resident microbiota of the intestine. Probiotic bacteria are considered as a safe solution for modulation of diminished commensal composition and also as influencer of the immune system in preventing allergic disorders [59]. Lactic acid bacteria and

bifidobacteria are good candidates as probiotics with an appropriate life span, no toxic or pathogenic properties, and no inflammatory induction. The selection of the bacteria as probiotics is mainly based on no harmful side effects during the history of their use for a long time. Consumption of these probiotics aid in balancing the ratio of the intestinal flora, avoiding the inhabiting of the pathogens by preventing the binding of them to the host cells, and suppressing the inflammation, which all are as the result of immune system regulation [60]. The effects of probiotics vary with the dose, strain, and duration of consumption and timing.

But the problem of the probiotics is their longevity and residence in the body of the host, as it was seen that they only remain during the administration period and not after that, showing the transient colonization of the probiotics [61–65].

Long-term effects of probiotics in different periods of everyone's life need to be more investigated in complementary studies.

As it was mentioned, immune tolerance is one of the necessary immune reactions to stop excessive inflammatory reactions. Preservation of this tolerance involves the integrity of the epithelial barrier that is heightened by commensal anaerobes, such as *Clostridium* spp. [15, 16, 66, 67], *Bacteroides fragilis* [68], and *Clostridium* spp. [66, 67], which are potent inducers, persuading Foxp3þ Treg differentiation to maintain mucosal tolerance and intestine integrity. Clostridia class also has adaptation properties in the intestinal cells to the routine exposure of an extended range of the antigens. This adaptation is acquired by the effect of IL-22 secreted by innate lymphoid cells which control enterocyte proliferation, activating the secretion of the mucus and antimicrobial production [16, 69].
