The Interaction Between Inflammatory Bowel Disease And Food Allergy In Animal Model

Food allergy is a global food safety issue.With a wide range of clinical symptoms,food allergy typically presents with digestive,cutaneous,mucosal,and respiratory manifestations,mostly triggered during gastrointestinal digestion.Recent advances in our understanding of food allergy have revealed that gastrointestinal diseases may increase the sensitivity and prevalence of food allergy.While in recent years,Inflammatory bowel disease(IBD)has emerged as a growing global public health threat affecting the gastrointestinal tract.Epidemiological data indicate that food allergy and IBD share many similarities in epidemiology,pathogenesis,clinical course,and treatment methods.In addition,IBD patients often display concurrent allergic conditions,indicating a potential comorbidity between IBD and food allergy via shared pathological and physiological mechanisms.Furthermore,the incidence rates of IBD and food allergy are on the rise in both developed and developing countries.Despite providing insights into the relationship between IBD and food allergy,epidemiological studies are limited in their ability to elucidate the intricate mechanisms underlying their mutual influence,highlighting the need for more comprehensive research.This study aims to use BALB/c mouse models to investigate the potential impact of IBD on food allergy and the potential impact of food allergy on IBD,using the positive correlation between their incidence.The study can provide scientific evidence for a better understanding of the interrelationship between IBD and food allergy,which can guide the prevention and control of these diseases.The main methods,results,and conclusions are as follows:(1)Three types of DSS induced IBD model were used in BALB/c mice.To construct a food allergy model,ovalbumin(OVA)and calcipotriene(MC903)were utilized in mice with IBD.Disease activity index(DAI),survival rate,weight loss,allergic reactions,and changes in intestinal tissue structure were observed and detected in each group.The 4%DSS-induced acute colitis model had a survival rate of 0,which did not adhere to the principles of replacement,reduction,and refinement(3R)in animal experiments.However,both the chronic colitis model and the 3%DSS-induced acute colitis model avoided high mortality rates and showed the most relevant symptoms of IBD and food allergies.Since the chronic colitis model better reflects the relapse-remission process in clinical patients and has a higher survival rate,we suggest using the chronic colitis model to establish a food allergy model in IBD mice.(2)BALB/c mice were used to established DSS-induced acute and chronic IBD mouse models.The DAI and body weight changes of the IBD mice were evaluated to determine the success of the IBD model establishment.Subsequently,changes in food allergy-related risk factors in the IBD mice were quantitatively analyzed by collecting serum,spleen tissue,and intestinal tissue.It was found that severe goblet cell loss,inflammatory lymphocyte infiltration,and neutrophil infiltration occurred in the colon tissue of IBD mice compared to the control group.Furthermore,the frequency of Tregs cells in CD4+cells decreased in the MLN of IBD mice,while the levels of MMCP-1 and histamine in mouse serum and Th2-type cytokines in spleen cell culture supernatant were decreased.Therefore,IBD may impair intestinal tolerance to food antigens by disrupting the structure of colon tissue and downregulating the frequency of Tregs in the MLN.Additionally,IBD may also reduce food allergy reactions in the IBD mice by downregulating the levels of Th2-type cytokines and MMCP-1.(3)Using the previously constructed food allergy model in IBD mice,mice were stimulated with OVA and clinical allergic symptoms were observed.After testing for OVA-specific antibodies and MMCP-1 levels in mouse serum and cytokine levels secreted by spleen cells,it was found that IBD reduced the IL-4 levels in mouse spleen cells,which subsequently lowered the concentrations of IgE and MMCP-1 in the serum and alleviated clinical allergy symptoms in mice.However,by observing changes in intestinal tissue structure and measuring cytokine and tight junction protein expression levels in jejunal tissue,IBD was found to promote intestinal damage and neutrophil infiltration in mice,and upregulate the IL-33 gene expression level in jejunal tissue,thereby potentially exacerbating intestinal symptoms of food allergy.Subsequently,examination of the mouse fecal microbiota revealed that IBD significantly decreased the richness of the intestinal microbiota and changed the structure of the gut microbiota.Therefore,the impact of IBD on food allergy is bidirectional.On the one hand,IBD can reduce allergic reactions and allergy symptoms by downregulating humoral immunity in food allergy.On the other hand,IBD can also disrupt intestinal tolerance to food antigens by damaging intestinal tissue structure and causing intestinal dysbiosis.(4)The chicken egg allergen OVA was selected as the model allergen to construct a food allergy model.By evaluating clinical allergic symptoms and detecting OVAspecific IgE and MMCP-1 levels in mouse serum,it was found that the mice in the food allergy modeling group exhibited significantly higher food allergy symptoms and OVA-specific IgE and MMCP-1 levels in serum compared to other groups,confirming the successful establishment of the food allergy model.Then,the evaluation of cytokine gene expression levels,mucins,and tight junction proteins in colonic tissues revealed that food allergy enhanced the intestinal barrier function of mice by down-regulating gene expression levels of pro-inflammatory cytokines IL-6,IL-1β,and IFN-γ,and upregulating gene expression levels of TGF-β and MUC2 in mice colon.This resulted in increased colon length and improved intestinal symptoms,suggesting that food allergy can alleviate IBD symptoms to a certain extent.In summary,this study found that there is a mutual interaction between IBD and food allergy.IBD can alleviate food allergy reactions by downregulating Th2 cytokines,while food allergy also exhibits a tendency to alleviate IBD symptoms.However,our study also discovered the ambivalent effect of IBD on food allergy,as it can potentially impair intestinal tolerance to food antigens through damage to intestinal tissue structure and dysbiosis of gut microbiota while reducing food allergy reactions.