A recent study published in Nature Materials has unveiled a groundbreaking oral immunotherapy platform that utilizes inulin gel combined with food allergens to effectively suppress food allergy responses and reduce the risk of anaphylactic shock. This innovative approach aims to deliver dietary antigens directly to intestinal dendritic cells, thereby modulating the immune response and promoting sustained oral tolerance.
Food allergies have become a significant health concern, particularly in industrialized nations, where accidental exposure can lead to severe reactions, including hypovolemic shock. Traditional management strategies have primarily focused on strict avoidance of allergens, experimental therapies, and emergency interventions for anaphylaxis. The first oral immunotherapy drug approved by the U.S. Food and Drug Administration (FDA), Palforzia, aims to reduce the severity of peanut allergies, yet nearly 20% of patients discontinue treatment due to gastrointestinal side effects. Additionally, challenges like inconsistent dosing and inadequate long-term desensitization have hindered effective management of food allergies.
Research indicates that food allergies may be linked to imbalances in the gut microbiome and the metabolites produced by gut microbes. Prior studies have shown that interventions such as probiotic therapy and fecal microbiota transplantation can promote allergen desensitization, underscoring the importance of gut health in allergy management.
The researchers sought to enhance the delivery of dietary allergens to the small intestine, where most tolerance to food allergens occurs. The inulin gel-based immunotherapy was designed to directly target dendritic cells in the small intestine, which are crucial for antigen sampling. Inulin, a prebiotic polysaccharide derived from plants, is not absorbed in the stomach and supports the growth of beneficial gut bacteria.
In the study, inulin was heated and cooled to form a gel, which was then combined with protein allergens such as ovalbumin from chicken egg whites and casein from bovine milk. Murine models sensitized to these allergens were treated with the inulin gel and protein allergen to assess the safety and efficacy of the therapy. Key parameters, including body weight, blood counts, and levels of immunoglobulin E (IgE), interferon-gamma (IFNγ), and various interleukins, were measured to evaluate the immune response and the potential for anaphylaxis.
To further investigate the immune mechanisms at play, the researchers employed single-cell RNA sequencing to analyze the immune landscape of the small intestinal lamina propria following treatment.
The findings revealed that the inulin gel-based oral immunotherapy effectively retained the allergen in the small intestine for extended periods, facilitating antigen uptake by dendritic cells. Notably, the mice that received the inulin gel with ovalbumin exhibited a sustained unresponsiveness to the allergen for over 13 weeks after treatment cessation.
In contrast, mice treated with ovalbumin and phosphate-buffered saline (PBS) displayed symptoms of anaphylactic shock, including a rapid decrease in body temperature. In stark contrast, those administered the inulin gel with ovalbumin experienced significantly reduced symptoms, no systemic hypothermia, and a lower incidence of allergic diarrhea.
The therapy also led to increased levels of regulatory T cells producing IFNγ and IL-10, which are known to suppress allergic responses. Moreover, the inulin gel treatment effectively reduced the production of pro-inflammatory cytokines IL-13 and IL-4, which are associated with allergic inflammation.
Importantly, the inulin gel-ovalbumin therapy normalized the dysregulated microbiome observed in the food allergy mouse models, restoring the abundance of beneficial bacteria such as Enterorhabdus and Eggerthellaceae.
Conclusions
This study demonstrates that an oral immunotherapy regimen utilizing inulin gel and protein allergens like ovalbumin or casein can be effectively retained in the small intestine, leading to immune responses that suppress allergic inflammation and the risk of anaphylactic shock. The sustained protective effects observed after discontinuation of therapy highlight the potential of this innovative approach in managing food allergies, paving the way for future clinical applications.
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