Roles of the dynamic gut microbiota and their associated immunoregulatory effects for successful oral immunotherapy treatment

Abstract

Abstract Background: We previously demonstrated that patients with IgE-mediated food allergy (FA) have a unique gut microbial signature. Objectives: To characterize the changes to the gut microbiome populations and putative immunoregulatory effects, associated with successful OIT. Methods: Stool samples were collected at inception of treatment from 252 patients undergoing OIT, and from 58 non-allergic controls. Additional samples were collected at successful completion of treatment (n=66). Bacterial 16S rRNA gene sequences from extracted sample DNA were amplified by PCR, with microbial communities analyzed by QIIME2. Stool extracts were evaluated for allergen-specific IgA 2,and for their induction capability of immunoregulatory genes in a colonic epithelial line (Caco-2). Results: For all FA types, patients with higher initial allergen eliciting doses (ED) had microbiota populations significantly closer to that of controls, compared to more sensitive patients with lower ED (p<0.0001). The relative abundance of Prevotellaand Bacteroides/Firmicutesratio significantly varied during OIT progression, increasing towards controls. Post-OIT stool eluents induced mRNA expression of APRIL and ZO-1 in Caco-2 cells and allergen-specific IgA 2was significantly increased in post- vs pre-OIT eluents (p<0.01). In Transwell assays, heat killed Bacteroides fragilisdecreased FITC-dextran4 leakage across the epithelial layer. Conclusions: Gut microbiome populations are dynamic during OIT, possibly reflecting a recovery from a FA to a nonallergic state. Immunoregulatory changes and positive effects on epithelial cell integrity suggest causative roles for the gut microbiome in maintaining the desensitized state. Supported by a grant from the Israeli Science Foundation (1527/21)