Effects of the fermentation products of Agave Tequilana inulin on allergic inflammation and mast cell activation 2261171

Abstract Introduction Agave inulin is a fructose-based prebiotic found in Agave Tequilana blue var. Weber exclusively from Jalisco, Mexico. The consumption of prebiotics by microbiota generates fermentation products (FPs), such as short-chain fatty acids (SCFAs). SCFAs travel from the gut to the bloodstream, exerting multiple effects on the immune system. Type I hypersensitivity reactions (allergies) are initiated by allergen-induced immunoglobulin E (IgE), which binds to the high-affinity IgE receptor (FcεRI) at the surface of mast cells (MCs). A second exposure to the allergen (antigen, Ag), IgE/Ag conjugates, and promotes FcεRI crosslinking, activating a signaling cascade leading to MCs degranulation and the release of preformed mediators like β-hexosaminidase, inducing inflammation. Methods We administered Agave Tequilana inulin as an oral pretreatment to C57BL6/J mice and determined its effect in the passive cutaneous anaphylaxis (PCA) reaction. To evaluate the participation of FPs in the observed effects, mice feces were harvested and fermented with inulin under in vitro anaerobic conditions. FPs were then used to pretreat bone marrow mast cells (BMMCs) for 24h. The effects of one of the FPs were analyzed by performing long and short-term exposure of bone marrow-derived mast cells (BMMCs) to sodium Butyrate (Bt). Results Inulin consumption reduced inflammation in a dose-dependent manner, except at the highest concentration tested. FPs treatment reduced FcεRI-induced β-hexosaminidase release. A 24h-long Bt treatment decreased FcεRI-induced and phorbol-myristate acetate/A23187-induced degranulation of BMMCs. Bt treatment reduced FcεRI γ subunit protein expression and blunted calcium mobilization. Fifteen min-long exposure to Bt also reduced BMMCs degranulation, affected calcium mobilization, and increased tubulin acetylation. Conclusion Results suggest that Agave inulin consumption reduces allergic inflammation through the production of FPs that modify the FcεRI signaling system. Funding Source SECIHTI, Cinvestav Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)