Clinical And Basic Research On The Relationship Between Allergic Rhinitis And Gut Microecology In Children

Background:Allergic rhinitis(AR)is a common allergic disease in children.Its incidence rate has been on the rise globally in recent years.The main symptoms are sneezing,runny nose,nasal congestion,itching and other symptoms after inhalation of allergens.Ig E-mediated anaphylaxis is the most common clinical anaphylaxis,but the etiology of allergic rhinitis is not fully understood.Many studies have shown that the maturity of a child’s immune system is closely linked to gut microecology.Changes such as delayed colonization of gut flora,structural disorders and reduced diversity can affect the host’s immune homeostasis and tolerance formation,which can lead to allergic diseases such as food allergy and atopic dermatitis.However,there are few studies on the relationship between AR in children and gut microecology at home and abroad.At the same time,based on the important role of gut microbiota in the pathogenesis of allergic diseases,targeted intestinal microbiota strategy has a good prospect for the treatment of allergic diseases.Fecal microbiota transplantation(FMT)refers to the transplantation of gut microecology from healthy donors to the recipient’s intestine,and the treatment of related diseases by restoring the intestinal flora of the recipient.Currently,FMT was effective in treating gastrointestinal diseases such as clostridium difficile infection and atopic dermatitis,but few studies have reported on fecal bacteria transplantation for AR.Based on the above background,we conducted clinical and basic studies on the relationship between AR and gut microecology.The gut microecology changes in children with AR were analyzed by collecting feces and performing 16 S r RNA detection.Through ovalbumin(OVA)induction,AR mice model was established to simulate AR in children,AR mice were treated with FMT,and to explore the therapeutic effect of FMT on AR mice.Objectives :To investigate the changes of gut microecology in children with AR.Explore the therapeutic effect of FMT on AR in mice,and further explore the effect of FMT on gut microflora in mice.Methods:Clinical Research Segments:1)Study design: Prospective,cross-sectional,and observational studies;2)Subjects: children with AR and healthy children(control group)(3-14 years of age)who attended the Children’s Outpatient Clinic at Xijing Hospital between August and November 2022;3)General data collection: birth history,feeding history,family history,medication history,diet habits,symptom score(TNSS score,QOL score,VAS score),Allergen and Fe NO,Immunoglobulin and blood tests,etc;4)Test index: 16 Sr RNA high-throughput sequencing was used to detect the intestinal flora.Basic Research Segments:1)4-week-old female BALB/c mice were sensitized and stimulated with OVA to establish the model of AR;2)The nasal mucosa of mice were stained histologically;3)The nasal lavage fluid of mice was collected and carry out Reich-Giemsa staining,and count the white blood cells by classification;4)The serum of mice was collected and the expression levels of OVA specific antibodies Ig E,IL-4,IFN-γ,IL-10 were detected;5)16S r RNA high-throughput sequencing was used to detect the intestinal flora of mice.Results:Clinical Research Segments:24 children with AR and 25 healthy control children were included in the clinical study.Compared with healthy control children,the diversity of intestinal microflora in children with AR was significantly reduced.In terms of bacterial composition,at the phylum level,the abundance of Bacteroidetes in children with AR was higher than that in the control group,and was significantly positively correlated with TNSS;At the family level,the abundance of Enterobacteriaceae in children with AR was higher than that in the control group,and there was a significant positive correlation with TNSS,EOS and t Ig E;At the genus level,the abundance of Agathobacter,Roseburia and Subdoligranum in children with AR were lower than those in the control group,and were significantly negatively correlated with TNSS,EOS,t Ig E,QOL and Fe NO.Basic Research Segments:Basic research found that the AR mice showed obvious nasal symptoms,with obvious infiltration of inflammatory cells in the nasal mucosa,irregular arrangement of pseudostratified ciliated columnar epithelial cells,necrosis and shedding of epithelial cells,and more eosinophils and neutrophils infiltration in the lamina propria.Compared with the control group,the body weight of AR were decreased significantly during the stimulation phase,the percentage of eosinophils in nasal lavage fluid increased significantly,and the levels of OVA-s Ig E and IL-4 in serum increased significantly,IFN-γ and IL-10 levels were significantly reduced.After FMT treatment,the nasal symptoms were relieved,the inflammation was reduced,the weight loss was not obvious,the percentage of eosinophils in nasal lavage fluid was significantly reduced,the levels of OVA-s Ig E and IL-4 were significantly redu,IFN-γ and IL-10 levels increased significantly.The results of intestinal microflora detection showed that the diversity of intestinal microflora in AR mice decreased,and the composition of microflora at the level of phylum,family and genus changed significantly.After FMT treatment,the diversity of intestinal microflora in mice increased,and the composition of intestinal microflora was also closed to the healthy state at all levels.Spearman correlation analysis showed that the change of intestinal microflora was significantly correlated with Th1/Th2 levelsConclusion:This study found that compared with healthy children,children with AR have unique characteristics of intestinal flora,with reduced diversity and significant changes in flora composition.At the same time,the diversity of intestinal flora in mice with AR decreased,and the composition of flora at the level of phylum,family and genus also changed significantly compared with the control group.FMT can reverse the change of intestinal flora in mice with AR and make the flora close to the healthy state.Affecting Th1/Th2 balance and improve IFN-γ And IL-10 level by restoring intestinal microflora,promote the formation of immune tolerance,and play a therapeutic role in AR mice.