The Screening And Mechanisms Of Probiotic Strains On Alleviation Of Food Allergy

Food allergy is a immune disorder caused by food protein antigens.In recent years,the prevalence of food allergy has been increasing in North America,Europe,Asia,and other regions,and the incidence of China is rising rapidly.Food allergy may cause one or more symptoms including gastrointestinal tract,skin,and respiratory tract,all of which have a significant impact on the quality of life of food allergy sufferers.The most common treatments for food allergy including rigorous avoidance of allergen-containing foods and desensitization therapy.As a result of the ineffective management of food allergen labelling and the risk of desensitization therapy,researchers have begun to investigate other treatments such as probiotic strains for food allergy.The “hygiene hypothesis” revealed the link between microorganisms and allergy disease,and the literature survey showed that the gastrointestinal tract is one of the most main way for food allergens’ exposure to the body.Gut microbiota was closely related with the occurrence and development of food allergy.Food allergy can alter the diversity and composition of gut microbiota.As a result,probiotic strains can be used as an effective way to alleviate food allergy.At present,there have been studies on the use of probiotic strains to alleviate host food allergy,and mainly focus on regulating T helper 1(Th1)/Th2 immune balance,increasing the proportion of Treg to improve oral immune tolerance,enhancing the integrity of intestinal barrier,etc.However,studies on the mechanism and material basis of probiotic strains regulating Th1/Th2 balance to alleviate food allergy are still insufficient and lacking relatively clear description,and there are few studies on the relationship between food allergy and gut metabolism.Based on the above background,a mouse model of food allergy was established in this study to screen effective probiotic strains which could alleviate food allergy.Then,we analyzed the gut microbiota and metabolites of mice feces by using 16 S r RNA amplification sequencing technology and untargeted metabolomics technology,and explored their possible mechanism and material basis.Finally,the possible mechanism and material basis were verified by animal experiments.The main research results are as follows:Firstly,BALB/c mice were used to establish a food allergy mouse model.The probiotic strains that could effectively alleviate food allergy in mice were selected by weight change,allergic symptoms,jejunum histopathological section,the levels of serum ovalbumin(OVA)-specific immunoglobulin E(Ig E)(68.07% 、 65.27% 、 60.89% reduction respecively),histamine(HIS)(22.68%、36.16%、30.51% reduction respecively),Th2-type cytokines(IL-4:50.50%、44.10%、42.27%;IL-5: 52.53%、40.63%、5.63%;IL-13: 52.54%、46.23%、28.42%)in the supernatant of jejunum.The results showed that Lactiplantibacillus plantarum CCFM1189,Limosilactobacillus reuteri CCFM1190,and Bifidobacterium longum CCFM1029 could alleviate weight loss,allergic symptoms and jejunum tissue damage in food allergy mice,reduce the levels of serum OVA-specific Ig E and HIS in the supernatant of jejunum,and regulate the immune balance of Th1/Th2 to alleviate the symptoms of food allergy mice.It was preliminarily believed that Lactiplantibacillus plantarum CCFM1189,Limosilactobacillus reuteri CCFM1190,and Bifidobacterium longum CCFM1029 are effective strains for alleviating food allergy in mice,but their mechanism and material basis need to be further explored.Secondly,16 S r RNA sequencing and untargeted metabolomics were used to analyze the diversity and composition of fecal gut microbiota and differential metabolites in mice,and explored the possible mechanism and material basis of the effective probiotic strains.Food allergy modeling decreased the diversity of gut microbiota in mice,and increased the abundance of Staphylococcus and Escherichia.The effective strains CCFM1189,CCFM1190,and CCFM1029 improved the community structure of gut microbiota.CCFM1189 increased the abundance of Akkermansia,which has anti-inflammatory effect.CCFM1190 improved the abundance of Faecalibaculum,which might effect the immune function of host.CCFM1029 increased the abundance of Bifidobacterium and some short-chain fatty acids(SCFAs)producing bacteria such as Dubosiella and Anaerovorax.Meanwhile,CCFM1189 and CCFM1190 increased the content of indoleacrylic acid(IA)in fecal samples of mice,which was related to the action of intestinal mucous layer.It was found that CCFM1189 and CCFM1190 were not able to metabolize tryptophan to produce IA by themselves in vitro fermentation experiment.Based on the above findings,IA may be an effective substance for alleviating food allergy,and CCFM1189 and CCFM1190 may effect by affecting gut microbiota to produce IA,but the specific mechanism of action remains to be further studied.Finally,mice were treated with antibiotics to eliminate the influence of some commensal microbiota to verify whether CCFM1189 and CCFM1190 produced IA by affecting the commensal microbiota.Meanwhile,the effect of IA on alleviating food allergy was studied.The results showed that CCFM1189 and CCFM1190 alleviated pathological symptoms of food allergy(body weight,allergy symptom score,diarrhea index and jejunum injury),and regulated Th1/Th2 immune balance and intestinal barrier integrity in food allergy mice by affecting commensal microbiota to produce IA.IA could relieve food allergy in mice to some content.For CCFM1029,by comparing the content of aryl hydrocarbon receptor(Ah R)in jejunum of mice,it was speculated that CCFM1029 might alleviate food allergy in mice by affecting aryl hydrocarbon receptor(Ah R)signaling pathway.Therefore,GNF351,the inhibitor of Ah R,was used to treat food allergy mice.The results showed that GNF351 inhibited CCFM1029 in alleviating weight loss,diarrhea and allergic symptoms,the levels of serum OVA-specific Ig E,HIS and Th2-type cytokines in the supernatant of jejunum of food allergy mice.CCFM1029 alleviated food allergy by affecting Ah R signaling pathway.