Probiotic Bacteria in Microbiome against Allergy

*Najaf Allahyari Fard, Zakie Mazhary and Nahid Javanshir*

### **Abstract**

According to the World Allergy Organization (WAO), approximately 20% of the global population suffers from allergies. As per ongoing investigations, their pervasiveness is expanding comprehensively. Allergic diseases are significant because of the high prevalence and constant increase in their costs and adverse effects on human life. Probiotics are proposed as an intervention for the prevention and treatment of allergic diseases. Various mechanisms are considered for the anti-allergic effects of probiotic properties, like detecting related molecular patterns, including DNA motifs or lipopolysaccharides (LPS) of the bacteria, through interaction with host immune systems by Toll-like receptors. In this chapter, the microbiome, allergy, and the role of immunomodulatory probiotics against allergy are discussed.

**Keywords:** probiotic, microbiome, allergy

#### **1. Introduction**

In industrialized countries, more than 20% of the population has symptoms of allergies. The commonness of childhood asthma increased by 50% in the USA from 1980 to 2000. The allergy mechanism is an immune response to the allergen, which is often mediated by the immunoglobulin E (IgE) antibody [1]. Allergies can be a serious risk for individuals. Allergens or pollens represent a small fraction of the proteins that humans are regularly exposed to. The importance of the topic in the uncertainty is the cause of the B and T cells' responses to these proteins [2, 3]. Notably, some proteins that are structurally similar pollens may lead to immune response, known as cross-reactivity [4].

The human body microbiome has a diverse composition of bacteria, archaea, fungi, protozoa, and viruses, which are inhabited mainly in the different epidermal surfaces of the body—the skin and mucosal surface. Some of the species of these microbiotas are identified based on cultural techniques, but due to limitations of these techniques [5], it is suggested that the number of human microbiota exceeds 1000 species or 10 times the number of cells in the entire body with 30 times larger total genome than the human genome.

A majority of these microbiotas are in the gastrointestinal tract, the major source of microbial exposure, and live in symbiosis with their host cells [6, 7]. Given up genes necessary for the survival of the commensal microbiota in other microenvironments and retained genes beneficial for the host with no or little benefit to themselves [8] are the evidences of the symbiotic coevolution of the microbiota and human [9].

The interplay of the immune system with gut microbiota starts from the day of birth and even before that. Early exposure during plasticity and prenatal period

seems to be beneficial to prevent the T helper cell type-2 (Th2)-mediated allergic disease [10]. Th2 phenotype is the dominant one in newborns [11] to prevent rejection in utero. Skewing to Th2 in the immune system leads to the stimulated secretion of IgE by B cells and hence to allergies as seen in germ-free mice with the same condition that results in greater IgE responses to food antigens and failure in producing the proper amount of regulatory T cell (Treg) responses [12–14]. On the other hand, upsurge in the amount of T helper cell type-1 (Th1) also mediates the autoimmune disease [12, 15–19].

Restoring Th1/Th2 is the significant role of the microbiota [20]. The association of microbiota and the immune system is mutual. This engagement results in different signaling pathways through the immune system's molecules that increase immune responses [21]. These regulations are crucial for maintaining the homeostasis of the host and for the prevention of different diseases by inducing secretion of IgA and regulatory T cell (Treg) and stimulation of tolerance in face of common antigens [22]. So the formation, maintenance, and heterogeneity of microbiota are necessary during early life owing to their regulatory and tolerance properties in the immune system [23, 24], as it was confirmed that the lack of microflora during a short time in early life results in defection in immune regulation [15]. The mechanisms of oral tolerance which are necessary to suppress excessive immune reactions to antigens are mediated by Foxp3þ Treg [25] and IgA, which is known as the most abundant immunoglobulin and is vital in establishing the composition of microbiota [26] and strengthening the mucosal barrier function [27].

Although, it is observed that abnormal IgA responses lead to allergy development [28]. So the obligation of equilibrium of the allergy mediators is more sensible now.

Lack of genetic elements such as Toll-like receptors that cause enterocyte proliferation like TLR4 and CD14, which enhance the detection of bacterial LPS by TLR4, and TLR9, which identify the genetic molecules of the microorganisms, also increase susceptibility to allergies [29, 30].

As the priority of the microbiome is proven, some factors are mentioned as follows, to support their presence and diversity in the body. Mode of birth; surgical or natural delivery, the process of contacting microflora in the first moment of the presence. Breast or formula feeding; the extension of contact with microflora. Nutritional patterns; the habit of food, based on people's patterns to eat fatty and fast foods or healthy ones like prebiotics which are considered beneficial for even the microbiota of the host. Antibiotics; the matter of using antibiotics at an early age or the trouble of overuse of them in all ages which impair normal flora. Locality; living in urban areas with all of the stresses, less interaction with nature in contrast with living in rural areas results in losing ancient commensal microbiota. Environmental factors; contacting people or animals. Hygiene; the obsession behaviors or normal ones. Lifestyle; the matter of activity or sedentariness in someone's lifestyle.

Natural delivery and breastfeeding are the first two initial and essential exposures when the immune system is not still mature and needs antigens to active oral tolerance [18, 25, 31]. Contravention of these simple factors grounds reformed patterns of early settlement which may result in the incidence of allergy [32]. Food sensitization especially milk allergy and atopic eczema are examples of reduced gut microbial diversity [33–37].
