Exogenous β-Hydroxybutyrate Supplementation Alleviates Ana o 3-Induced Allergic Responses.

Exogenous BHB supplementation mitigated the drop in body temperature associated with Ana o 3-induced allergic responses in mice.

• Body temperature drop is a key indicator of systemic anaphylaxis in the mouse model.
• BHB supplementation attenuated this temperature decline compared to the allergic control group.
• The model used Ana o 3, a major cashew nut allergen, to induce allergic reactions.

Exogenous BHB significantly reduced levels of Ana o 3-specific IgE in sensitized mice.

• Ana o 3-specific IgE is a primary biomarker of allergic sensitization.
• Reduction in specific IgE levels indicates a dampening of the allergic immune response.
• BHB is the main effector molecule of the ketogenic diet and was administered exogenously.

Exogenous BHB supplementation significantly reduced serum MCPT-1 levels in Ana o 3-sensitized mice.

• MCPT-1 (mouse mast cell protease-1) is a biomarker of mast cell activation and degranulation.
• Reduction in MCPT-1 indicates suppression of mast cell-mediated allergic responses.
• This finding suggests BHB acts at the level of mast cell activation.

Omics analyses indicated that exogenous BHB may exert antiallergic effects through downregulation of Fc receptor expression on mast cells.

• Fc receptors on mast cells bind IgE and trigger degranulation upon allergen cross-linking.
• Downregulation of Fc receptor expression would reduce mast cell responsiveness to allergen-IgE complexes.
• This mechanism was identified through omics-level analyses (transcriptomic and/or metabolomic approaches).

Omics analyses suggested that BHB reduces harmful metabolites as part of its antiallergic mechanism.

• Metabolomic analysis identified reductions in harmful metabolites associated with BHB treatment.
• This metabolite modulation represents a second proposed mechanism alongside Fc receptor downregulation.
• The combination of transcriptomic and metabolomic ('Omics') analyses was used to characterize mechanistic pathways.

The ketogenic diet's main effector, BHB, was evaluated as a potential intervention strategy for cashew nut allergy using an Ana o 3-induced mouse model.

• Cashew allergy incidence has been increasing alongside rising consumption levels.
• Effective therapeutic strategies for cashew allergy remain limited.
• The ketogenic diet has demonstrated immunomodulatory effects across various diseases.
• Ana o 3 is a major cashew nut allergen used to sensitize and challenge the mouse model.