A healthy mucosal immune system allows people living in everyday environments to inhale airborne particles or consume dietary proteins without experiencing abnormal reactions. The mucosal immune system is a large and complex system of internal environmental stability and immune response consisting of the mucosal epithelium or mucosa-associated lymphoid tissue (MALT). Another sustaining factor is the microbiota system (resident probiotic flora). Of the known mucosal immune structures, the most clinically relevant are the respiratory mucosa and the intestinal mucosa immune mechanisms. The main tissue structures of interest are the gut-associated mucosal system (GAMS) or gut-associated lymphoid-like tissue (GALT), nasopharyngeal-associated lymphoid-like tissue (NALT, distributed in 30.1% of the upper nasal cavity, 2.9% of the sinuses, 2.6% of the nasal septum, 14.1% of the epiglottis, 10.4% of the posterior turbinate, 26.4% of the middle turbinate, 13.5% of the inferior turbinate), larynx-associated lymphoid tissue ( LALT) and bronchial-associated lymphoid tissue (BALT). Others are the mammary gland, salivary and lacrimal glands, genital tract, and inner ear. Any disruption of structures, including imbalance of the microbiota, will lead to the development of allergy and allergy-related symptoms. In this article, we will briefly describe the association of mucosal immune tissues associated with the pediatric respiratory and intestinal tracts with disease. Basic components and functions of the mucosal immune system The distribution of mucosal immune tissues is not isolated; they are closely related to each other and functionally relevant. In the respiratory tract, mucosal defense mechanisms depend on the mechanical clearance of mucosal surface cilia and the initiation and maintenance of antigen presentation by mucosal epithelial cells involved in inflammatory cell chemotaxis or activation. In alveoli lacking mucosal cilia, the immune response is dependent on intra-alveolar macrophages. Of note is the relationship between inducible trachea-associated lymphoid tissue (iBALT), which is widely distributed in the bronchi, perivascular and intrapulmonary interstitial formations, and immune-mediated tissue injury in some pathological states. A specific mucosal structural region, the laryngeal mucosa, is the intersection of the IgG-dominant region of the lower respiratory tract and the IgA-dominant region of the digestive tract. In contrast to the lower respiratory tract, a unique flora normally distributed in this region plays an important role in the mucosal immune response of the CD1d-NKT cell axis. A clinical example of a related mechanism is laryngopharyngeal reflux (LPR). In the GI tract, the prominent tissue structure is the Peyer’s lymph node (PP), which serves as the first line of defense, and immune exclusion from the mucosal surface is effective in preventing antigen neutralization by the intestinal epithelium; especially important is the antigen-selective process mediated by membrane-like cells (M cells), where antigens (e.g., euthermia, poliovirus, poliomyelitis, etc.) are not present. （The tissue difference between BALT and GALT is that the former lacks M cells, but in pathological states with increased amounts of antigen, BALT and alveoli can induce epithelial differentiation to produce M cells. Early life, especially the first postnatal year, is an important stage in the transition from infancy to maturity of adaptive immunity, including mucosal immunity, and a vulnerable stage for allergic disorders in infants and children. The elucidation of the underlying mechanisms by which respiratory submucosal lymphocytes and GALT (BALT, NALT, and GALT) constitute the mucosal IgA response sensing and effector sites, separately or together, will both contribute to the understanding of certain diseases, such as food intolerance, inflammatory bowel disease, chronic inflammatory or allergic diseases of the respiratory tract, rheumatoid and other autoimmune diseases, and will also influence the development of new concepts of treatment. Mucosal immune system and allergenicity After antigen capture by the respiratory mucosa in healthy individuals, airway mucosal dendritic cells (AMDCs) and other antigen-presenting cells (APCs) complete the processing of pathogenic and non-pathogenic agents through a T-cell-mediated immune response, leaving the respiratory mucosa in its original state of stability (homeostasis). This stabilization, once disrupted, will lead to abnormal respiratory allergic responses, as demonstrated in antigen capture assays in the experimental allergic airway disease (EAAD) model mouse. As in asthma, the underlying impairment is dominated by a paracrine T lymphocyte subpopulation (Th2) shift, but the processing of non-pathogenic allergens is mediated by CD4+ T cells to form an inflammatory response. Susceptibility to allergens is governed by two important conditions: environmental and genetic factors. There is a specific relationship between commensal microorganisms in the digestive tract and allergy. in GALT, a Th2 regulatory cell dominance is presented due to antigenic stimulation of bacteria in the intestinal lumen, defending against intestinal inflammation formation. In response to TLR4-dependent signaling and antigenic stimulation by non-invasive commensal flora, GALT forms complex lymphocyte responses and Th1-offset memory effector cells, which suppress the allergic response to food antigens. Once this effect is absent, oral immune tolerance (oraltolerance) induction will not develop and Th2 cell-mediated hyperresponsiveness can occur. Oral immune tolerance is a fundamental feature of mucosal immunophysiology and involves a myriad of immunological mechanisms. Its integrity is inextricably linked to allergic disorders, which have heterogeneous manifestations and an interrelated clinical disease spectrum. Indeed, the immune response associated with the intestinal mucosa is not confined to local or rarely causes a systemic immune response. Pediatricians often hear the typical complaint that my child has a sudden exacerbation of asthma after ingesting a certain food. This is typical of the association of gastrointestinal and respiratory symptoms. There are also diet and skin allergic diseases, etc. Another common clinical presentation in pediatrics is chronic cough and ENT problems (allergic rhinitis, sinusitis, adenoid hyperplasia, etc.) following respiratory viral infections. This so-called allergic inflammation of the upper and lower respiratory tract derives from the basic understanding of a systemic (respiratory) disease and is a fundamental point of immunology for anti-allergic treatment. And the intrinsic relationship between the local immune effects of the mucosa and the systemic immune response, constituted by the association between the mucosal immune systems of the respiratory-digestive tract, is no longer just a speculation (Figure 1). As seen in Figure 1, lung intrinsic dendritic cells (antigen-presenting cells) capture allergens (inhaled pollen). Allergens stimulate the maturation of dendritic cells (DCs) and promote the proliferation of allergen-specific T cells in secondary lymphoid-like organs. Subsequently, these allergen-specific T cells enter the lung to form the primary pathophysiological stage of allergen response together with antigen-presenting cells loaded with abundant allergens. Normally, the regulatory T cell (Treg) network prevents the development of excessive airway allergic T cell responses. Inhaled pollen can also be swallowed into the digestive tract due to the inherent anatomy of the sinus and upper airway mucosal layers that can retain fine environmental particles. In healthy states, ingested allergens are processed by gastrointestinal antigen-presenting cells, and the anti-inflammatory environment of the gastrointestinal tract converts these antigen-presenting cells into regulatory antigen-presenting cells (DCr) and promotes the proliferation of allergen-response-specific Treg cells. The microbial flora has an important role in the maintenance and formation of this anti-inflammatory environment and disturbance of normal homeostasis, including increasing yeast colonization and blocking the enhancement of Treg response to allergens. In the gastrointestinal tract, one potential signaling molecule composition produced through host and microbial actions is oxidized lipids (oxylipins). While host genetics may modulate specific responses by altering the intrinsic recognition response, antibiotics and diet can alter the balance of the microbial flora to produce a disordered response. Clinical studies on the spectrum of mucosal immune-related diseases are more focused on food intolerance-associated eczema, chronic respiratory diseases and IgA deficiency-associated diseases and chronic inflammatory bowel disease. Therefore, adjustment of abnormal oral immune tolerance is also a positive direction for future treatment. Experimental animal studies revealed that the level of antigen-specific S-IgA antibodies in the intestine can affect food allergenicity in experimental rats, while antigen-specific CD3+ cells in Peyer’s pooled lymph nodes promote IgA production by releasing IL-10 and TGF-β, which increase the number of secreted antigen-specific IgA cells. It is suggested that S-IgA plays a role in the mechanism of food tolerance. Gut microbiota – an important factor in the physiological regulation of mucosal immunity It is well known that the physiological regulation of immunity in the gut mucosa depends on the establishment of its healthy microbiota, i.e., the microflora hypothesis. Although the complex nature of allergic diseases with strong heterogeneous manifestations needs to be deeply understood, it is known that an intact mucosal barrier allows the host to avoid or reduce allergic disorders caused by allergic factors in the environment. Thus, the maintenance of healthy flora becomes the physiological basis for targeted therapy (Figure 2). Several diseases have already benefited from treatment by modifying the flora in the pathological state. The anti-allergic potential of these probiotic flora is strain-specific, strain-product-specific and host-specific, and the correct selection of age-related populations can yield beneficial results. For example, Lactobacillus or Bacillus emulsions are very effective in improving atopic eczema and milk-induced allergic reactions in infancy but not in asthma attacks. Relevant points: firstly, the age of the host. In younger children, a rapid i.e. inductive response of the nasal mucosa to microbial stimuli that does not occur in adults can occur through a TLR-dependent process In vitro experiments have found that nasal mucosa treated with bacterial lipopolysaccharide and allergens hinders allergic inflammation of the nasal mucosa due to the conversion of lipopolysaccharide from Th2 to Th1 through local immune response and enhanced intensity of IL-10 expression for anti-inflammatory responses. This phenomenon, however, does not occur in adults. As a probiotic hypothesis, targeting asthma has not been proven, perhaps beneficial for the asthmatic population with significant GI problems. Secondly, the target of probiotic therapy for allergic disorders remains to be studied in depth. This depends mainly on the specificity of the strain and the type of host allergic disorder disease. Third, the potential of probiotics to transport antigens is related to the degree of protein hydrolysis in food. Moderately hydrolyzed proteins not only stimulate humoral immunity in the gut, but also induce oral immune tolerance, as antigen breakdown is an essential component of mucosal tolerance formation. Finally, strain specificity has been demonstrated in earlier interventional studies. For example, two different strains of L. rhamnosus have completely different roles in rotavirus diarrhea. From the above, it is clear that the role of strains and the role of ingested protein hydrolysis cannot be ignored when emphasizing the role of mucosal immunobiology in allergic disorders, and that age factors are important in influencing the development of allergic disorders in infancy and early childhood. Antibiotics-microbiota-mucosal immunity-allergic diseases In this chain of four relationships, the relationship between antibiotics and allergic diseases was once reduced to drug allergy, thus ignoring the large and complex known and unknown nature of the intermediate links. Although no clear conclusions can be drawn from common infantile eczema, asthma and asthma-like symptoms (asthma-like symptoms), some findings are already suggesting that the frequency of antibiotic use early in life is associated with subsequent childhood allergic diseases or states (eczema, asthma and asthma-like symptoms) not only in terms of risk, but also in terms of antibiotic type is associated. A cohort study involving 13,116 children from the first year of life to 7 years of age showed that the administration of antibiotics to children with non-respiratory infections was associated with a significantly higher incidence of asthma than the respiratory infection population (OR 1.86, 95% CI 1.02-3.37), especially over 4 courses (OR 1.46, 95% CI 1.14-1.88), and more prominently in rural children. The high frequency and duration of broad-spectrum cephalosporin antibiotic use was more prevalent in these susceptible children. However, it remains to be seen whether the risk index for allergic disease decreases after reducing broad-spectrum cephalosporin antibiotics. A recent analysis from Canada involving a cohort of 251,817 cases born from 1997-2003 from the neonatal period to early childhood compared perinatal factors with birth physical and environmental factors, and relative risk factors between otitis media, bronchitis, upper respiratory tract infections, and lower respiratory tract infections in the late postnatal year 1 antibiotic-exposed population （The results of the analysis of the prevalence of asthma (hazard ratio, HR) in the first year of life (2-9 years) yielded the same suggestion (modified HR 1.12, 95% CI 1.08-1.16), with a prominent risk of exposure when the duration of antibiotic use was >4 courses (modified HR: 1.30, 95% CI 1.20-1.41); in the comparison of antibiotic types, macrolide antibiotic exposure The risk was particularly prominent in the comparison of antibiotic types (corrected HR: 1.11, 95% CI 1.06-1.17). It takes 12 weeks for structural damage to the intestinal mucosa to be repaired and for function to return to normal, which is a relatively long journey. In infants and young children (early in life), not only may symptoms of allergic disorders (eczema, hyperhidrosis, prolonged khat-like symptoms, etc.) occur during this period, but antibiotics lead to disruption of the intestinal microbiota (intestinal flora), which in turn affects the effectiveness of mucosal immunophysiology, especially with respect to oral immune tolerance. It is easy to understand that the frequency of antibiotic use in the early stages of infancy tends to rise with the allergic disorders thereafter: the result of structural disruption and functional deficiency of oral immune tolerance is one of the important causes. Conclusion In 1942, a 33-year-old woman in New Haven (New Haven) was critically ill with streptococcal sepsis …… However, she lived to the age of 99 and was saved by penicillin. 66 years later, a 70-year-old man in San Francisco (San Francisco) was infected with vancomycin-resistant faecal A 70-year-old man in San Francisco died of vancomycin-resistant Enterococcus faecalis, despite the best efforts of doctors. The widespread use of broad-spectrum antibiotics has forced humans to face the super challenge of bacterial resistance madness. The relative decrease in infectious diseases has been accompanied by a relative increase in the incidence of allergic diseases. It is the responsibility of all clinical pediatricians to emphasize and thoroughly investigate the role of the mucosal immune system in the formation of allergic diseases and to reduce the adverse factors affecting the mucosal immune system, including the judicious use of antibiotics.