Oral immunotherapy in combination with a non-digestible oligosaccharide supplemented diet in a peanut allergy mouse model

Background: Although the prevalence of food allergy is increasing, no curative treatment is available yet. Improving oral immunotherapy (OIT) for food allergy is necessary to reduce side effects and achieve tolerance. Non-digestible oligosaccharides, like scFOS/lcFOS (FF), have been shown to reduce allergic symptoms in murine models of allergy. This study aims to evaluate the capacity of FF to support OIT in an established peanut allergy mouse model. Method: After sensitization (d0-d35) using peanut extract (PE), mice received a 1% FF (9:1) or control diet for the rest of the study and were treated with PE or PBS intragastric (5 times/week) for three weeks (d41-d59). Hereafter, mice were exposed to PE via an intradermal (d64), intragastric (d70) and intraperitoneal (d77, i.p.) challenge to determine clinical efficacy (acute allergic skin responses, anaphylactic shock symptoms and body temperature). Furthermore, antibody levels, cytokine production and number of various immune cells were measured at different time points during the study (d0, d35, d50, d63, d71 and d78). Results: OIT on its own, was able to reduce allergic symptoms upon PE challenges, in addition, serum levels of IgE, IgG1 and IgG2a, were raised after OIT. OIT+FF was able to lower the acute allergic skin response and mast cell degranulation after peanut exposure. FF did not show an additive effect on antibody levels. On d63 and d78, the production of cytokines IL-5 and IL-10 by splenocytes, and on d63 by MLN cells was elevated in the OIT+FF group compared to the OIT group. After therapy (d63), percentage of B cells in the spleen was lower in the OIT+FF group compared to the OIT group. On d78, Th1 cells were higher in the MLN and Th2 cells were lower in the spleen in the OIT+FF group vs the OIT group. Also, activated CD8+ T cells were lower in the MLN and CD103+CD11b+ DCs were higher in the spleen. During therapy (d50), the short-chain fatty acid (SCFA) content in the caecum showed a shift by the FF diet, to a higher butyrate, lower acetate ratio. Conclusion: These data show that in a mouse model for peanut allergy, OIT+FF protect against allergic responses upon peanut exposure. However, the OIT dose seemed too low to protect against the i.p. challenge. Furthermore, cellular parameters suggest Th2 suppression after OIT+FF, compared to only OIT. FF also altered the cytokine production and influenced SCFA content in the caecum. In future experiments, we will focus more on the working mechanism.